KRAMARCZYK JACK (US)
O'NEILL JULIA (US)
ALTARAS NEDIM (US)
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WO2020061457A1 | 2020-03-26 | |||
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US201715674872A | 2017-08-11 |
GOMEZ-AGUADO ET AL.: "Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives", NANOMATERIALS, vol. 10, 2020, pages 264
WADHWA ET AL.: "Opportunities and Challenges in the Delivery of mRNA-Based Vaccines", PHARMACEUTICS, vol. 12, 2020, pages 102
STEPHEN F. ALTSCHUL ET AL.: "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs", NUCLEIC ACIDS RES., vol. 25, 1997, pages 3389 - 3402, XP002905950, DOI: 10.1093/nar/25.17.3389
SMITH, T.F.WATERMAN, M.S.: "Identification of common molecular subsequences", J. MOL. BIOL., vol. 147, 1981, pages 195 - 197, XP024015032, DOI: 10.1016/0022-2836(81)90087-5
NEEDLEMAN, S.B.WUNSCH, C.D.: "A general method applicable to the search for similarities in the amino acid sequences of two proteins", J. MOL. BIOL., vol. 48, 1970, pages 443 - 453
BERGE ET AL.: "describe pharmaceutically acceptable salts in detail", J. PHARMACEUTICAL SCIENCES, vol. 66, 1977, pages 1 - 19
CLAIMS What is claimed is: 1. An article, comprising: a liquid pharmaceutical composition comprising RNA formulated in a lipid nanoparticle, liposome, or lipoplex; and a label, suggesting an amount of the liquid pharmaceutical composition to be administered to a subject; wherein the article has a shelf-life of at least three months when stored at a temperature of greater than 0 °C and less than or equal to 10 °C; wherein the amount is greater than or equal to (1 + the fraction of the RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the liquid pharmaceutical composition); and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. 2. The article of claim 1, wherein the article comprises a total amount of full length RNA, and the total amount of full length RNA is greater than or equal to (1 + the fraction of the full length RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the full length RNA) x (the number of individual doses of the liquid pharmaceutical composition in the article). 3. An article, comprising: a liquid pharmaceutical composition comprising RNA formulated in a lipid nanoparticle, liposome, or lipoplex; wherein the article has a shelf-life of at least three months when stored at a temperature of greater than 0 °C and less than or equal to 10 °C; wherein the article comprises a total amount of full length RNA, and the total amount of full length RNA is greater than or equal to (1 + the fraction of the full length RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the full length RNA) x (the number of individual doses of the liquid pharmaceutical composition in the article); and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. 4. The article of any of the preceding claims, wherein the article comprises a vial, a syringe, a cartridge, an infusion pump, and/or a light protective container. 5. The article of any preceding claims, wherein the amount is greater than or equal to 1.05 x (an individual dose of the liquid pharmaceutical composition), such as greater than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition). 6. The article of any preceding claim, wherein the RNA is encapsulated within the lipid nanoparticle, liposome, or lipoplex. 7. The article of any preceding claim, wherein the lipid nanoparticle, liposome, or lipoplex comprises a lipid nanoparticle. 8. An article, comprising: a liquid pharmaceutical composition comprising an RNA encoding one or more human cytomegalovirus (hCMV) antigens formulated in a lipid carrier housed in a container; wherein the container comprises a total amount of RNA and wherein the total amount of RNA includes 40%-95% intact RNA and 5%-60% RNA that is less than full length RNA. 9. The article of claim 8, wherein the percentage of intact RNA is greater than or equal to 15% + the percentage of intact RNA that would degrade in the liquid pharmaceutical composition over a shelf-life of the article. 10. The article of claim 8 or 9, wherein the article comprises at least 5% more intact RNA than an effective dose of the intact RNA. 11. An article, comprising: a liquid pharmaceutical composition comprising an RNA formulated in a lipid carrier housed in a container; and a label on the container, wherein the label identifies a number of individual doses of the liquid pharmaceutical composition housed in the container, an amount of each individual dose of the liquid pharmaceutical composition to be administered to a subject, and an effective dose of RNA within the liquid pharmaceutical composition within each individual dose, wherein the container comprises a total amount of RNA, wherein the total amount of RNA has a value of at least the number of individual doses in the container times 5% greater than the amount of the effective dose of RNA within each individual dose; and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. 12. The article of claim 11, wherein the container comprises a total amount of full length RNA, wherein the total amount of full length RNA is at least the number of individual doses in the container times 5% greater than the amount of the effective dose of full length RNA within each individual dose. 13. The article of any one of claims 8-12, wherein the article has a shelf-life of at least three months when stored at a temperature of greater than 0 °C and less than or equal to 10 °C. 14. The article of any one of claims 8-13, wherein the RNA is encapsulated within the lipid carrier. 15. The article of any one of claims 8-14, wherein the lipid carrier comprises a lipid nanoparticle. 16. The article of any preceding claim, wherein the RNA comprises mRNA. 17. The article of any preceding claim, wherein the RNA comprises greater than or equal to 400, 500, 1000, 2000, 3000, 4000, 5000, 6000, 7000, or 8000 nucleotides. 18. The article of any preceding claim, wherein the RNA comprises less than or equal to 15,000, 14,000, 13,000, 12,000, 11,000, 10,000, 9000, 8000, 7000, or 6000 nucleotides. 19. The article of any preceding claim, wherein the liquid pharmaceutical composition is formulated in an aqueous solution. 20. The article of any preceding claim, wherein the one or more hCMV antigens comprises greater than or equal to 1 and less than or equal to 6 hCMV antigens. 21. The article of any preceding claim, wherein the RNA comprises a nucleotide sequence having at least 80% identity, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. 22. The article of any preceding claim, wherein the RNA comprises a nucleotide sequence having at least 90% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. 23. A pharmaceutical composition comprising mRNA encapsulated in a lipid nanoparticle, wherein the composition comprises a total amount of intact mRNA that is greater than an effective amount of intact mRNA, wherein the composition comprises at least the effective amount of the intact mRNA after storage of the composition for a period of time; and wherein the mRNA encodes one or more human cytomegalovirus (hCMV) antigens. 24. The pharmaceutical composition of claim 23, wherein the total amount of intact mRNA decreases in the composition after storage of the composition for the period of time. 25. The pharmaceutical composition of claim 23 or 24, wherein the total amount of intact mRNA is calculated to account for degradation of the intact mRNA during the storage of the composition for the period of time. 26. The pharmaceutical composition of claim 25, wherein the degradation is from transesterification of the intact mRNA. 27. The pharmaceutical composition of claim 25 or 26, wherein the degradation is greater than or equal to 5%, greater than or equal to 7%, greater than or equal to 8%, greater than or equal to 9%, greater than or equal to 10%, or greater than or equal to 12% of the total mRNA in the composition per month. 28. The pharmaceutical composition of any one of claims 23-27, wherein the period of time is greater than or equal to 1 month, greater than or equal to 2 months, greater than or equal to 3 months, greater than or equal to 6 months, or greater than or equal to 9 months. 29. The pharmaceutical composition of any one of claims 23-28, wherein the storage is at a temperature of from about 0°C to about 10°C, such as at about 5°C. 30. The pharmaceutical composition of any one of claims 23-29, wherein the total amount of intact mRNA is at least 40%, such as at least 50%, at least 55%, at least 60%, at least 63%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% of the total mRNA in the composition. 31. The pharmaceutical composition of any one of claims 23-30, wherein the effective amount of intact mRNA is at least about 15%, such as at least about 18%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, or at least about 55% of the total mRNA in the composition. 32. The pharmaceutical composition of any one of claims 23-31, wherein the pharmaceutical composition comprises at least 50% intact mRNA of the total mRNA in the composition following storage of the composition for 3 months at about 5°C. 33. The pharmaceutical composition of any one of claim 23-32, wherein the effective amount of intact mRNA comprises at least 5 micrograms of the intact mRNA, such as at least 10 micrograms, at least 20 micrograms, at least 30 micrograms, at least 40 micrograms, at least 50 micrograms, at least 60 micrograms, at least 70 micrograms, at least 80 micrograms, at least 90 micrograms, at least 100 micrograms, at least 125 micrograms, or at least 150 micrograms of the intact mRNA. 34. The pharmaceutical composition of any one of claims 23-33, wherein the one or more hCMV antigens comprises greater than or equal to 1 and less than or equal to 6 hCMV antigens. 35. The pharmaceutical composition of any one of claims 23-34, wherein the mRNA comprises a nucleotide sequence having at least 80% identity, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. 36. The pharmaceutical composition of any one of claims 23-35, wherein the mRNA comprises a nucleotide sequence having at least 90% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. 37. A container (such as a vial, a syringe, a cartridge, an infusion pump, and/or a light protective container) comprising the pharmaceutical composition of any one of claims 23-36. 38. An article of any one of claims 1-22, wherein the pharmaceutical composition is the pharmaceutical composition of any one of claims 23-36. 39. A method of filling an article, comprising: adding RNA formulated in a lipid nanoparticle, liposome, or lipoplex to the article to form an amount of a liquid pharmaceutical composition in the article; wherein the amount is greater than or equal to (1 + the fraction of the RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the liquid pharmaceutical composition) x (the number of individual doses in the article); and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. 40. The method of claim 39, wherein the adding RNA formulated in a lipid nanoparticle, liposome, or lipoplex to the article forms an amount of full length RNA in the article, and wherein the amount of full length RNA is greater than or equal to (1 + the fraction of the full length RNA that would degrade in the liquid pharmaceutical composition over the shelf- life of the article) x (an individual dose of the full length RNA) x (the number of individual doses in the article). 41. The method of any one of claims 39-40, wherein the RNA and/or lipid nanoparticle are frozen prior to addition to the article. 42. The method of any one of claims 39-41, wherein the article is stored at a temperature of greater than 0 °C and less than 10 °C for up to 1 year. 43. The method of any one of claims 39-42, wherein at least 40% of the amount of the RNA in the liquid pharmaceutical composition is intact if stored for three months at a temperature of greater than 0 °C and less than 10 °C. 44. The method of any one of claims 39-43, wherein the liquid pharmaceutical composition comprises the pharmaceutical composition of any one of claims 23-36. 45. The method of any one of claims 39-44, wherein the lipid nanoparticle, liposome, or lipoplex comprises a lipid nanoparticle. 46. A method of delivering an effective dose of an RNA to a subject, comprising; administering a liquid pharmaceutical composition comprising an RNA formulated in a lipid carrier to a subject, wherein a total dose of the RNA is administered to the subject, and wherein the total dose of RNA administered to the subject is at least 5% greater than an effective dose of the RNA; and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. 47. The method of claim 46, wherein the lipid carrier comprises a lipid nanoparticle. 48. The method of any one of claims 39-47, wherein the one or more hCMV antigens comprises greater than or equal to 1 and less than or equal to 6 hCMV antigens. 49. The method of any one of claims 39-48, wherein the RNA comprises a nucleotide sequence having at least 80% identity, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. 50. The method of any one of claims 39-49, wherein the RNA comprises a nucleotide sequence having at least 90% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. 51. A method of compensating for transesterification of mRNA in a composition comprising the mRNA encapsulated by a lipid nanoparticle, the method comprising preparing the composition with increased mRNA purity as compared to an mRNA purity that will be present in the composition after storage of the composition, such that the amount of mRNA present in the composition after storage will comprise an effective amount of the mRNA, and wherein the mRNA encodes one or more human cytomegalovirus (hCMV) antigens. 52. The method of claim 51, wherein the composition comprises the pharmaceutical composition of any one of claims 23-36. 53. The method of any one of claims 51-52, wherein the one or more hCMV antigens comprises greater than or equal to 1 and less than or equal to 6 hCMV antigens. 54. The method of any one of claims 51-53, wherein the mRNA comprises a nucleotide sequence having at least 80% identity, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. 55. The method of any one of claims 51-54, wherein the mRNA comprises a nucleotide sequence having at least 90% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. |
In some embodiments, the ionizable amino lipid is salt thereof. The central amine moiety of a lipid according to Formula (VIII), (VIIIa1), (VIIIa2), (VIIIa3), (VIIIa4), (VIIIa5), (VIIIa6), (VIIIa7), or (VIIIa8) may be protonated at a physiological pH. Thus, a lipid may have a positive or partial positive charge at physiological pH. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein: R 1 is optionally substituted C 1 -C 24 alkyl or optionally substituted C 2 -C 24 alkenyl; R 2 and R 3 are each independently optionally substituted C1-C36 alkyl; R 4 and R 5 are each independently optionally substituted C 1 -C 6 alkyl, or R 4 and R 5 join, along with the N to which they are attached, to form a heterocyclyl or heteroaryl; L 1 , L 2 , and L 3 are each independently optionally substituted C1-C I 8 alkylene; G 1 is a direct bond, -(CH 2 )nO(C=O)-, -(CH 2 )n(C=O)O-, or -(C=O)-; G 2 and G 3 are each independently -(C=O)O- or -0(C=O)-; and n is an integer greater than 0. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein: G 1 is -N(R 3 )R 4 or -OR 5 ; R 1 is optionally substituted branched, saturated or unsaturated C12-C36 alkyl; R 2 is optionally substituted branched or unbranched, saturated or unsaturated C 12 -C 36 alkyl when L is -C(=O)-; or R 2 is optionally substituted branched or unbranched, saturated or unsaturated C4-C36 alkyl when L is C6-C12 alkylene, C6-C12 alkenylene, or C2-C6 alkynylene; R 3 and R 4 are each independently H, optionally substituted branched or unbranched, saturated or unsaturated C 1 -C 6 alkyl; or R 3 and R 4 are each independently optionally substituted branched or unbranched, saturated or unsaturated C1-C6 alkyl when L is C6-C12 alkylene, C6- C12 alkenylene, or C2-C6 alkynylene; or R 3 and R 4 , together with the nitrogen to which they are attached, join to form a heterocyclyl; R 5 is H or optionally substituted C1-C6 alkyl; L is -C(=O)-, C6-C 12 alkylene, C6-C12 alkenylene, or C2-C6 alkynylene; and n is an integer from 1 to 12. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt thereof, wherein: each R la is independently hydrogen, R lc , or R ld ; each R lb is independently R lc or R ld ; each R 1c is independently –[CH 2 ] 2 C(O)X 1 R 3 ; each R ld Is independently -C(O)R 4 ; each R 2 is independently -[C(R 2a ) 2 ]cR 2b ; each R 2a is independently hydrogen or C1-C6 alkyl; R 2b is -N(L 1 -B) 2 ; -(OCH 2 CH 2 ) 6 OH; or -(OCH 2 CH 2 ) b OCH 3 ; each R 3 and R 4 is independently C6-C30 aliphatic; each I.3 is independently C1-C10 alkylene; each B is independently hydrogen or an ionizable nitrogen-containing group; each X 1 is independently a covalent bond or O; each a is independently an integer of 1-10; each b is independently an integer of 1-10; and each c is independently an integer of 1-10. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein: X is N, and Y is absent; or X is CR, and Y is NR; -SC(=O)R 1 , -NR a C(=O)R 1 , -C(=O)NR b R c , -NR a C(=O)NR b R c , -OC(=O)NR b R c , or -NR a C(=O)OR 1 ; L 2 is -O(C=O)R 2 , -(C=O)OR 2 , -C(=O)R 2 , -OR 2 , -S(O)xR 2 , -S-SR 2 , -C(=O)SR 2 , -SC(=O)R 2 , -NR d C(=O)R 2 , -C(=O)NR e R f , -NR d C(=O)NR e R f , -OC(=O)NR e R f ; -NR d C(=O)OR 2 or a direct bond to R 2 ; G 1 and G 2 are each independently C 2 -C 12 alkylene or C 2 -C 12 alkenylene; G 3 is C1-C24 alkylene, C2-C24 alkenylene, C1-C24 heteroalkylene or C2-C24 heteroalkenylene when X is CR, and Y is NR; and G 3 is C 1 -C 24 heteroalkylene or C 2 -C 24 heteroalkenylene when X is N, and Y is absent; R a , R b , R d and R e are each independently H or C1-C12 alkyl or C1-C12 alkenyl; R c and R f are each independently C 1 -C 12 alkyl or C 2 -C 12 alkenyl; each R is independently H or C 1 -C 12 alkyl; R 1 , R 2 and R 3 are each independently C1-C24 alkyl or C2-C24 alkenyl; and x is 0, 1 or 2, and wherein each alkyl, alkenyl, alkylene, alkenylene, heteroalkylene and heteroalkenylene is independently substituted or unsubstituted unless otherwise specified. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein: L 1 and L 2 are each independently -0(C=0)-, -(C=0)0-, -C(=0)-, -0-, -S(0)x- s -S-S-, -C(=0)S-, -SC(=0)-, -NR a C(=0)-, -C(=0)NR a -, -NR a C(=0)NR a -, -OC(=0)NR a -, -NR a C(=0)0- or a direct bond; G 1 is C,-C 2 alkylene, -(C=0)-, -0(C=0)-, -SC(=0)-, -NR a C(=0)- or a direct bond; G 2 is -C(0)-, -(CO)O-, -C(=0)S-, -C(=0)NR a - or a direct bond; G 3 is C1-C6 alkylene; R a is H or C 1 -C 12 alkyl; R l a and R lb are, at each occurrence, independently either: (a) H or C1-C12 alkyl; or (b) R la is H or C1-C12 alkyl, and R I b together with the carbon atom to which it is bound is taken together with an adjacent R l b and the carbon atom to which it is bound to form a carbon-carbon double bond; R 2a and R 2b are, at each occurrence, independently either: (a) H or C1-C12 alkyl; or (b) R 2a is H or C 1 -C 12 alkyl, and R 2b together with the carbon atom to which it is bound is taken together with an adjacent R 2b and the carbon atom to which it is bound to form a carbon-carbon double bond; R 3a and R 3b are, at each occurrence, independently either (a): H or C1-C12 alkyl; or (b) R 3a is H or C 1 -C 12 alkyl, and R 3b together with the carbon atom to which it is bound is taken together with an adjacent R and the carbon atom to which it is bound to form a carbon-carbon double bond; R 4A and R 4B are, at each occurrence, independently either: (a) H or C1-C12 alkyl; or (b) R 4A is H or C 1 -C 12 alkyl, and R 4B together with the carbon atom to which it is bound is taken together with an adjacent R 4B and the carbon atom to which it is bound to form a carbon-carbon double bond; R 5 and R 6 are each independently H or methyl; R 7 is H or C,-C 20 alkyl; R 8 is OH, -N(R 9 )(C=0)R 10 , -(C=0)NR 9 R 10 , -NR 9 R 10 , -(C=0)0R" 1 or -0(C=0)R", provided that G 3 is C4-C6 alkylene when R 8 is -NR 9 R 10 , R 9 and R 10 are each independently H or C 1 -C 12 alkyl; R" is aralkyl; a, b, c and d are each independently an integer from 1 to 24; and x is 0, 1 or 2, wherein each alkyl, alkylene and aralkyl is optionally substituted. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein: X and X' are each independently N or CR; Y and Y' are each independently absent, -O(C=O)-, -(C=O)O- or NR, provided that: a) Y is absent when X is N; b) Y' is absent when X' is N; c) Y is -O(C=O)-, -(C=O)O- or NR when X is CR; and d) Y' is -O(C=O)-, -(C=O)O- or NR when X' is CR, L 1 and L 1' are each independently -O(C=O)R', -(C=O)OR' , -C(=O)R', -OR 1 , -S(O)zR', -OC(=O)NR b R c or -NR a C(=O)OR'; L 2 and L 2’ are each independently -O(C=O)R 2 , -(C=O)OR 2 , -C(=O)R 2 , -OR 2 , -S(O)zR 2 , -S-SR 2 , -C(=O)SR 2 , -SC(=O)R 2 , -NR d C(=O)R 2 , -C(=O)NR e R f , -NR d C(=O)NR e R f , -OC(=O)NR e R f ;-NR d C(=O)OR 2 or a direct bond to R 2 ; G 1 . G 1’ , G 2 and G 2’ are each independently C2-Ci2 alkylene or C2-C12 alkenylene; G is C2-C24 heteroalkylene or C2-C24 heteroalkenylene; R a , R b , R d and R e are, at each occurrence, independently H, C 1 -C 12 alkyl or C 2 -C 12 alkenyl; R c and R f are, at each occurrence, independently C1-C12 alkyl or C2-C12 alkenyl; R is, at each occurrence, independently H or C 1 -C 12 alkyl; R 1 and R 2 are, at each occurrence, independently branched C 6 -C 24 alkyl or branched C6-C24 alkenyl; z is 0, 1 or 2, and wherein each alkyl, alkenyl, alkylene, alkenylene, heteroalkylene and heteroalkenylene is independently substituted or unsubstituted unless otherwise specified. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein: L 1 is -O(C=O)R 1 , -(C=O)OR 1 , -C(=O)R 1 , -OR 1 , -S(O) x R 1 , -S-SR 1 , - C(=O)SR 1 , -SC(=O)R 1 , -NR a C(=O)R 1 , -C(=O)NR b R c , -NR a C(=O)NR b R c , -OC(=O)NR b R c or -NR a C(=O)OR 1 ; L 2 is -O(C=O)R 2 , -(C=O)OR 2 , -C(=O)R 2 , -OR 2 , -S(O)xR 2 , -S-SR 2 , - C(=O)SR 2 , -SC(=O)R 2 , -NR d C(=O)R 2 , -C(=O)NR e R f , -NR d C(=O)NR e R f , -OC(=O)NR e R f ; -NR d C(=O)OR 2 or a direct bond to R 2 ; G 1 and G 2 are each independently C2-C12 alkylene or C2-C12 alkenylene; G 3 is C 1 -C 24 alkylene, C 2 -C 24 alkenylene, C 3 -C 8 cycloalkylene or C 3 -C 8 cycloalkenylene; R a , R b , R d and R e are each independently H or C 1 -C 12 alkyl or C 1 -C 12 alkenyl; R c and R f are each independently C1-C12 alkyl or C2-C12 alkenyl; R 1 and R 2 are each independently branched C 6 -C 24 alkyl or branched C 6 - C 24 alkenyl; R 3 is -N(R 4 )R 5 ; R 4 is C1-C12 alkyl; R 5 is substituted C1-C12 alkyl; and x is 0, 1 or 2, and wherein each alkyl, alkenyl, alkylene, alkenylene, cycloalkylene, cycloalkenylene, aryl and aralkyl is independently substituted or unsubstituted unless otherwise specified. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein: L 1 is -O(C=O)R 1 , -(C=O)OR 1 , -C(=O)R 1 , -OR 1 , -S(O)xR 1 , -S-SR 1 , -C(=O)SR 1 , -SC(=O)R 1 , -NR a C(=O)R 1 , -C(=O)NR b R c , -NR a C(=O)NR b R c , -OC(=O)NR b R c or -NR a C(=O)OR 1 ; L 2 is -O(C=O)R 2 , -(C=O)OR 2 , -C(=O)R 2 , -OR 2 , -S(O)xR 2 , -S-SR 2 , -C(=O)SR 2 , -SC(=O)R 2 , -NR d C(=O)R 2 , -C(=O)NR e R f , -NR d C(=O)NR e R f , -OC(=O)NR e R f ;-NR d C(=O)OR 2 or a direct bond to R 2 ; G 1a and G 2b are each independently C2-C12 alkylene or C2-C12 alkenylene; G 1b and G 2b are each independently C1-C12 alkylene or C2-C12 alkenylene; G 3 is C 1 -C 24 alkylene, C 2 -C 24 alkenylene, C 3 -C 8 cycloalkylene or C 3 -C 8 cycloalkenylene; R a , R b , R d and R e are each independently H or C 1 -C 12 alkyl or C 2 -C 12 alkenyl; R c and R f are each independently C1-C12 alkyl or C2-C12 alkenyl; R 1 and R 2 are each independently branched C6-C24 alkyl or branched C6- C24 alkenyl; R 3a is -C(=O)N(R 4a )R 5a or -C(=O)OR 6 ; R 3b is -NR 4b C(=O)R 5b ; R 4a is C1-C12 alkyl; R 4b is H, C 1 -C 12 alkyl or C 2 -C 12 alkenyl; R 5a is H, C1-C8 alkyl or C2-C8 alkenyl; R 5b is C2-C12 alkyl or C2-C12 alkenyl when R 4b is H; or R 5b is C1-C12 alkyl or C2-C12 alkenyl when R 4b is C 1 -C 12 alkyl or C 2 -C 12 alkenyl; R 6 is H, aryl or aralkyl; and x is 0, 1 or 2, and wherein each alkyl, alkenyl, alkylene, alkenylene, cycloalkylene, cycloalkenylene, aryl and aralkyl is independently substituted or unsubstituted. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein: G 1 is -OH, - R 3 R 4 , -(C=0) R 5 or - R 3 (C=0)R 5 ; G 2 is -CH 2 - or -(C=0)-; R is, at each occurrence, independently H or OH; R 1 and R 2 are each independently optionally substituted branched, saturated or unsaturated C 12 -C 36 alkyl; R 3 and R 4 are each independently H or optionally substituted straight or branched, saturated or unsaturated Ci-C6 alkyl; R 5 is optionally substituted straight or branched, saturated or unsaturated Ci-C6 alkyl; and n is an integer from 2 to 6. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein: one of G 1 or G 2 is, at each occurrence, -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -S(O) , -S-S-, -C(=O)S-, SC(=O)-, -N(R a )C(=O)-, -C(=O)N(R a )-, -N(R a )C(=O)N(R a )-, -OC(=O)N(R a )- or -N(R a )C(=O)O-, and the other of G 1 or G 2 is, at each occurrence, -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -S(O) , -S-S-, -C(=O)S-, -SC(=O)-, -N(R a )C(=O)-, -C(=O)N(R a )-, -N(R a )C(=O)N(R a )-, -OC(=O)N(R a )- or -N(R a )C(=O)O- or a direct bond; L is, at each occurrence, ~O(C=O)-, wherein ~ represents a covalent bond to X; X is CR a ; Z is alkyl, cycloalkyl or a monovalent moiety comprising at least one polar functional group when n is 1; or Z is alkylene, cycloalkylene or a polyvalent moiety comprising at least one polar functional group when n is greater than 1; R a is, at each occurrence, independently H, C 1 -C 12 alkyl, C 1 -C 12 hydroxylalkyl, C 1 -C 12 aminoalkyl, C 1 -C 12 alkylaminylalkyl, C 1 -C 12 alkoxyalkyl, C 1 -C 12 alkoxycarbonyl, C 1 -C 12 alkylcarbonyloxy, C1-C12 alkylcarbonyloxyalkyl or C1-C12 alkylcarbonyl; R is, at each occurrence, independently either: (a) H or C 1 -C 12 alkyl; or (b) R together with the carbon atom to which it is bound is taken together with an adjacent R and the carbon atom to which it is bound to form a carbon-carbon double bond; R 1 and R 2 have, at each occurrence, the following structure, respectively: a 1 and a 2 are, at each occurrence, independently an integer from 3 to 12; b 1 and b 2 are, at each occurrence, independently 0 or 1; c 1 and c 2 are, at each occurrence, independently an integer from 5 to 10; d 1 and d 2 are, at each occurrence, independently an integer from 5 to 10; y is, at each occurrence, independently an integer from 0 to 2; and n is an integer from 1 to 6, wherein each alkyl, alkylene, hydroxylalkyl, aminoalkyl, alkylaminylalkyl, alkoxyalkyl, alkoxycarbonyl, alkylcarbonyloxy, alkylcarbonyloxyalkyl and alkylcarbonyl is optionally substituted with one or more substituent. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein: -C(=O) R a -, , R a C(=O) R a -, -OC(=O) R a - or -NR a C(=O)O- or a direct bond; G 1 and G 2 are each independently unsubstituted C1-C12 alkylene or C1-C12 alkenylene; G 3 is C 1 -C 24 alkylene, C 1 -C 24 alkenylene, C 3 -C 8 cycloalkylene, C 3 -C 8 cycloalkenylene; R a is H or C1-C12 alkyl; R 1 and R 2 are each independently C6-C24 alkyl or C6-C24 alkenyl; R 3 is H, OR 5 , CN, -C(=O)OR 4 , -OC(=O)R 4 or - R 5 C(=O)R 4 ; R 4 is C1-C12 alkyl; R 5 is H or C1-C6 alkyl; and x is 0, 1 or 2. In some embodiments, the lipid nanoparticle comprises a lipid having the structure:
or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein: L 1 and L 2 are each independently -0(C=0)-, -(C=0)0-, -C(=0)-, -0-, -S(0)x-, -S-S-, -C(=0)S-, -SC(=0)-, - R a C(=0)-, -C(=0) R a -, - R a C(=0) R a -, -OC(=0) R a -, - R a C(=0)0- or a direct bond; G 1 is Ci-C2 alkylene, - (C=0)-, -0(C=0)-, -SC(=0)-, - R a C(=0)- or a direct bond: G 2 is -C(=0)-, -(C=0)0-, -C(=0)S-, -C(=0)NR a - or a direct bond; G 3 is C1-C6 alkylene; R a is H or C1-C12 alkyl; R la and R lb are, at each occurrence, independently either: (a) H or C 1 -C 12 alkyl; or (b) R la is H or C 1 -C 12 alkyl, and R lb together with the carbon atom to which it is bound is taken together with an adjacent R lb and the carbon atom to which it is bound to form a carbon-carbon double bond; R 2a and R 2b are, at each occurrence, independently either: (a) H or C 1 -C 12 alkyl; or (b) R 2a is H or C1-C12 alkyl, and R 2b together with the carbon atom to which it is bound is taken together with an adjacent R 2b and the carbon atom to which it is bound to form a carbon-carbon double bond; R 3a and R 3b are, at each occurrence, independently either (a): H or C1-C12 alkyl; or (b) R 3a is H or C1-C12 alkyl, and R 3b together with the carbon atom to which it is bound is taken together with an adjacent R and the carbon atom to which it is bound to form a carbon-carbon double bond; R 4a and R 4b are, at each occurrence, independently either: (a) H or C1-C12 alkyl; or (b) R 4a is H or C1-C12 alkyl, and R 4b together with the carbon atom to which it is bound is taken together with an adjacent R 4b and the carbon atom to which it is bound to form a carbon-carbon double bond; R 5 and R 6 are each independently H or methyl; R 7 is C 4 -C 20 alkyl; R 8 and R 9 are each independently C 1 -C 12 alkyl; or R 8 and R 9 , together with the nitrogen atom to which they are attached, form a 5, 6 or 7-membered heterocyclic ring; a, b, c and d are each independently an integer from 1 to 24; and x is 0, 1 or 2. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein: L 1 and L 2 are each independently -0(C=0)-, -(C=0)0- or a carbon- carbon double bond; R la and R lb are, at each occurrence, independently either (a) H or C 1 -C 12 alkyl, or (b) R la is H or C1-C12 alkyl, and R lb together with the carbon atom to which it is bound is taken together with an adjacent R lb and the carbon atom to which it is bound to form a carbon-carbon double bond; R 2a and R 2b are, at each occurrence, independently either (a) H or C1-C12 alkyl, or (b) R 2a is H or C1-C12 alkyl, and R 2b together with the carbon atom to which it is bound is taken together with an adjacent R 2b and the carbon atom to which it is bound to form a carbon-carbon double bond; R 3a and R 3b are, at each occurrence, independently either (a) H or C1-C12 alkyl, or (b) R 3a is H or C 1 -C 12 alkyl, and R 3b together with the carbon atom to which it is bound is taken together with an adjacent R 3b and the carbon atom to which it is bound to form a carbon-carbon double bond; R 4a and R 4b are, at each occurrence, independently either (a) H or C 1 -C 12 alkyl, or (b) R 4a is H or C 1 -C 12 alkyl, and R 4b together with the carbon atom to which it is bound is taken together with an adjacent R 4b and the carbon atom to which it is bound to form a carbon-carbon double bond; R 5 and R 6 are each independently methyl or cycloalkyl; R 7 is, at each occurrence, independently H or C1-C12 alkyl; R 8 and R 9 are each independently unsubstituted C1-C12 alkyl; or R 8 and R 9 , together with the nitrogen atom to which they are attached, form a 5, 6 or 7- membered heterocyclic ring comprising one nitrogen atom; a and d are each independently an integer from 0 to 24; b and c are each independently an integer from 1 to 24; and e is 1 or 2, provided that: at least one of R la , R 2a , R 3a or R 4a is C 1 -C 12 alkyl, or at least one of L 1 or L 2 is -0(C=0)- or -(C=0)0-; and R la and R lb are not isopropyl when a is 6 or n-butyl when a is 8. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are the same or different, each a linear or branched alkyl with 1-9 carbons, or as alkenyl or alkynyl with 2 to 11 carbon atoms, L 1 and L 2 are the same or different, each a linear alkyl having 5 to 18 carbon atoms, or form a heterocycle with N, X 1 is a bond, or is -CG-G- whereby L2-CO-O-R 2 is formed, X 2 is S or O, L3 is a bond or a lower alkyl, or form a heterocycle with N, R3 is a lower alkyl, and R 4 and R 5 are the same or different, each a lower alkyl. In some embodiments, the lipid nanoparticle comprises an ionizable lipid having the structure: (XVII-L), or a pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: or a pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: (XX- L), or a pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: (XXVI-L), or a pharmaceutically acceptable salt thereof. In some embodiments, the lipid nanoparticle comprises a lipid having the structure: pharmaceutically acceptable salt thereof. Non-cationic lipids In certain embodiments, the lipid nanoparticles described herein comprise one or more non-cationic lipids. Non-cationic lipids may be phospholipids. In some embodiments, the lipid nanoparticle comprises 5-25 mol% non-cationic lipid. For example, the lipid nanoparticle may comprise 5-20 mol%, 5-15 mol%, 5-10 mol%, 10-25 mol%, 10-20 mol%, 10-25 mol%, 15-25 mol%, 15-20 mol%, or 20-25 mol% non-cationic lipid. In some embodiments, the lipid nanoparticle comprises 5 mol%, 10 mol%, 15 mol%, 20 mol%, or 25 mol% non-cationic lipid. In some embodiments, a non-cationic lipid of the disclosure comprises 1,2-distearoyl-sn- glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-gly cero- phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), l,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC), 1,2-diundecanoyl-sn-glycero-phosphocholine (DUPC), 1- palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-di-O-octadecenyl-sn-glycero-3- phosphocholine (18:0 Diether PC), 1-oleoyl-2 cholesterylhemisuccinoyl-sn-glycero-3- phosphocholine (OChemsPC), 1-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2- dilinolenoyl-sn-glycero-3-phosphocholine,1,2-diarachidonoyl- sn-glycero-3-phosphocholine, 1,2- didocosahexaenoyl-sn-glycero-3-phosphocholine, 1,2-diphytanoyl-sn-glycero-3- phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2- dilinoleoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinolenoyl-sn-glycero-3- phosphoethanolamine, 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine, 1,2- didocosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phospho-rac- (1-glycerol) sodium salt (DOPG), sphingomyelin, or mixtures thereof. In some embodiments, the lipid nanoparticle comprises 5 – 15 mol%, 5 – 10 mol%, or 10 – 15 mol% DSPC. For example, the lipid nanoparticle may comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 mol% DSPC. In certain embodiments, the lipid composition of the lipid nanoparticle composition disclosed herein can comprise one or more phospholipids, for example, one or more saturated or (poly)unsaturated phospholipids or a combination thereof. In general, phospholipids comprise a phospholipid moiety and one or more fatty acid moieties. A phospholipid moiety can be selected, for example, from the non-limiting group consisting of phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl glycerol, phosphatidyl serine, phosphatidic acid, 2-lysophosphatidyl choline, and a sphingomyelin. A fatty acid moiety can be selected, for example, from the non-limiting group consisting of lauric acid, myristic acid, myristoleic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha-linolenic acid, erucic acid, phytanoic acid, arachidic acid, arachidonic acid, eicosapentaenoic acid, behenic acid, docosapentaenoic acid, and docosahexaenoic acid. Particular phospholipids can facilitate fusion to a membrane. For example, a cationic phospholipid can interact with one or more negatively charged phospholipids of a membrane (e.g., a cellular or intracellular membrane). Fusion of a phospholipid to a membrane can allow one or more elements (e.g., a therapeutic agent) of a lipid-containing composition (e.g., LNPs) to pass through the membrane permitting, e.g., delivery of the one or more elements to a target tissue. Non-natural phospholipid species including natural species with modifications and substitutions including branching, oxidation, cyclization, and alkynes are also contemplated. For example, a phospholipid can be functionalized with or cross-linked to one or more alkynes (e.g., an alkenyl group in which one or more double bonds is replaced with a triple bond). Under appropriate reaction conditions, an alkyne group can undergo a copper-catalyzed cycloaddition upon exposure to an azide. Such reactions can be useful in functionalizing a lipid bilayer of a nanoparticle composition to facilitate membrane permeation or cellular recognition or in conjugating a nanoparticle composition to a useful component such as a targeting or imaging moiety (e.g., a dye). Phospholipids include, but are not limited to, glycerophospholipids such as phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, phosphatidylinositols, phosphatidy glycerols, and phosphatidic acids. Phospholipids also include phosphosphingolipid, such as sphingomyelin. In some embodiments, a phospholipid of the invention comprises 1,2-distearoyl-sn- glycero-3-phosphocholine (DSPC), 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dilinoleoyl-sn-glycero-3- phosphocholine (DLPC), 1,2-dimyristoyl-sn-gly cero-phosphocholine (DMPC), 1,2-dioleoyl-sn- glycero-3-phosphocholine (DOPC), l,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2- diundecanoyl-sn-glycero-phosphocholine (DUPC), 1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine (POPC), 1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine (18:0 Diether PC), 1-oleoyl-2 cholesterylhemisuccinoyl-sn-glycero-3-phosphocholine (OChemsPC), 1-hexadecyl- sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2-dilinolenoyl-sn-glycero-3-phosphocholine,1,2- diarachidonoyl-sn-glycero-3-phosphocholine, 1,2-didocosahexaenoyl-sn-glycero-3- phosphocholine, 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE), 1,2- distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinoleoyl-sn-glycero-3- phosphoethanolamine, 1,2-dilinolenoyl-sn-glycero-3-phosphoethanolamine, 1,2-diarachidonoyl- sn-glycero-3-phosphoethanolamine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG), sphingomyelin, or mixtures thereof. In certain embodiments, a phospholipid useful or potentially useful in the present invention is an analog or variant of DSPC. In certain embodiments, a phospholipid useful or potentially useful in the present invention is a compound of Formula (IX): (IX), or a salt thereof, wherein: each R 1 is independently optionally substituted alkyl; or optionally two R 1 are joined together with the intervening atoms to form optionally substituted monocyclic carbocyclyl or optionally substituted monocyclic heterocyclyl; or optionally three R 1 are joined together with the intervening atoms to form optionally substituted bicyclic carbocyclyl or optionally substitute bicyclic heterocyclyl; n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; A is of the formula: each instance of L 2 is independently a bond or optionally substituted C 1-6 alkylene, wherein one methylene unit of the optionally substituted C1-6 alkylene is optionally replaced with O, N(R N ), S, C(O), C(O)N(R N ), NR N C(O), C(O)O, OC(O), OC(O)O, OC(O)N(R N ), NR N C(O)O, or NR N C(O)N(R N ); each instance of R 2 is independently optionally substituted C 1-3 0 alkyl, optionally substituted C 1-3 0 alkenyl, or optionally substituted C 1-3 0 alkynyl; optionally wherein one or more methylene units of R 2 are independently replaced with optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, optionally substituted heteroarylene, N(R N ), O, S, C(O), C(O)N(R N ), NR N C(O), NR N C(O)N(R N ), C(O)O, OC(O), - OC(O)O, OC(O)N(R N ), NR N C(O)O, C(O)S, SC(O), C(=NR N ), C(=NR N )N(R N ), NR N C(=NR N ), NR N C(=NR N )N(R N ), C(S), C(S)N(R N ), NR N C(S), NR N C(S)N(R N ), S(O), OS(O), S(O)O, - OS(O)O, OS(O) 2 , S(O) 2 O, OS(O) 2 O, N(R N )S(O), S(O)N(R N ), N(R N )S(O)N(R N ), OS(O)N(R N ), N(R N )S(O)O, S(O) 2 , N(R N )S(O) 2 , S(O) 2 N(R N ), N(R N )S(O) 2 N(R N ), OS(O) 2 N(R N ), or - N(R N )S(O) 2 O; each instance of R N is independently hydrogen, optionally substituted alkyl, or a nitrogen protecting group; Ring B is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; and p is 1 or 2; provided that the compound is not of the formula: , wherein each instance of R 2 is independently unsubstituted alkyl, unsubstituted alkenyl, or unsubstituted alkynyl. In some embodiments, the phospholipids may be one or more of the phospholipids described in PCT Application No. PCT/US2018/037922. In some embodiments, the lipid nanoparticle comprises a molar ratio of 5-25% non- cationic lipid relative to the other lipid components. For example, the lipid nanoparticle may comprise a molar ratio of 5-30%, 5-15%, 5-10%, 10-25%, 10-20%, 10-25%, 15-25%, 15-20%, 20-25%, or 25-30% non-cationic lipid. In some embodiments, the lipid nanoparticle comprises a molar ratio of 5%, 10%, 15%, 20%, 25%, or 30% non-cationic lipid. In some embodiments, the lipid nanoparticle comprises a molar ratio of 5-25% phospholipid relative to the other lipid components. For example, the lipid nanoparticle may comprise a molar ratio of 5-30%, 5-15%, 5-10%, 10-25%, 10-20%, 10-25%, 15-25%, 15-20%, 20-25%, or 25-30% phospholipid. In some embodiments, the lipid nanoparticle comprises a molar ratio of 5%, 10%, 15%, 20%, 25%, or 30% phospholipid lipid. Structural Lipids The lipid composition of a pharmaceutical composition disclosed herein can comprise one or more structural lipids. As used herein, the term “structural lipid” includes sterols and also to lipids containing sterol moieties. Incorporation of structural lipids in the lipid nanoparticle may help mitigate aggregation of other lipids in the particle. Structural lipids can be selected from the group including but not limited to, cholesterol, fecosterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatidine, tomatine, ursolic acid, alpha-tocopherol, hopanoids, phytosterols, steroids, and mixtures thereof. In some embodiments, the structural lipid is a sterol. As defined herein, “sterols” are a subgroup of steroids consisting of steroid alcohols. In certain embodiments, the structural lipid is a steroid. In certain embodiments, the structural lipid is cholesterol. In certain embodiments, the structural lipid is an analog of cholesterol. In certain embodiments, the structural lipid is alpha-tocopherol. In some embodiments, the structural lipids may be one or more of the structural lipids described in U.S. Application No.16/493,814. In some embodiments, the lipid nanoparticle comprises a molar ratio of 25-55% structural lipid relative to the other lipid components. For example, the lipid nanoparticle may comprise a molar ratio of 10- 55%, 25-50%, 25-45%, 25-40%, 25-35%, 25-30%, 30-55%, 30-50%, 30-45%, 30-40%, 30-35%, 35-55%, 35-50%, 35-45%, 35-40%, 40-55%, 40-50%, 40-45%, 45-55%, 45- 50%, or 50-55% structural lipid. In some embodiments, the lipid nanoparticle comprises a molar ratio of 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or 55% structural lipid. In some embodiments, the lipid nanoparticle comprises 30-45 mol% sterol, optionally 35- 40 mol%, for example, 30-31 mol%, 31-32 mol%, 32-33 mol%, 33-34 mol%, 35-35 mol%, 35- 36 mol%, 36-37 mol%, 38-38 mol%, 38-39 mol%, or 39-40 mol%. In some embodiments, the lipid nanoparticle comprises 25-55 mol% sterol. For example, the lipid nanoparticle may comprise 25-50 mol%, 25-45 mol%, 25-40 mol%, 25-35 mol%, 25-30 mol%, 30-55 mol%, 30- 50 mol%, 30-45 mol%, 30-40 mol%, 30-35 mol%, 35-55 mol%, 35-50 mol%, 35-45 mol%, 35- 40 mol%, 40-55 mol%, 40-50 mol%, 40-45 mol%, 45-55 mol%, 45-50 mol%, or 50-55 mol% sterol. In some embodiments, the lipid nanoparticle comprises 25 mol%, 30 mol%, 35 mol%, 40 mol%, 45 mol%, 50 mol%, or 55 mol% sterol. In some embodiments, the lipid nanoparticle comprises 35 – 40 mol% cholesterol. For example, the lipid nanoparticle may comprise 35, 35.5, 36, 36.5, 37, 37.5, 38, 38.5, 39, 39.5, or 40 mol% cholesterol. Polyethylene Glycol (PEG)-Lipids The lipid composition of a pharmaceutical composition disclosed herein can comprise one or more polyethylene glycol (PEG) lipids. As used herein, the term “PEG-lipid” or “PEG-modified lipid” refers to polyethylene glycol (PEG)-modified lipids. Non-limiting examples of PEG-lipids include PEG-modified phosphatidylethanolamine and phosphatidic acid, PEG-ceramide conjugates (e.g., PEG-CerC14 or PEG-CerC20), PEG-modified dialkylamines, and PEG-modified 1,2-diacyloxypropan-3- amines. Such lipids are also referred to as PEGylated lipids. For example, a PEG lipid can be PEG-c-DOMG, PEG-DMG, PEG-DLPE, PEG-DMPE, PEG-DPPC, or a PEG-DSPE lipid. In some embodiments, the PEG-lipid includes, but not limited to 1,2-dimyristoyl-sn- glycerol methoxypolyethylene glycol (PEG-DMG), 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-N-[amino(polyethylene glycol)] (PEG-DSPE), PEG-disteryl glycerol (PEG-DSG), PEG-dipalmetoleyl, PEG-dioleyl, PEG-distearyl, PEG-diacylglycamide (PEG- DAG), PEG-dipalmitoyl phosphatidylethanolamine (PEG-DPPE), or PEG-l,2- dimyristyloxlpropyl-3-amine (PEG-c-DMA). In some embodiments, the PEG-lipid is selected from the group consisting of a PEG- modified phosphatidylethanolamine, a PEG-modified phosphatidic acid, a PEG-modified ceramide, a PEG-modified dialkylamine, a PEG-modified diacylglycerol, a PEG-modified dialkylglycerol, and mixtures thereof. In some embodiments, the PEG-modified lipid is PEG- DMG, PEG-c-DOMG (also referred to as PEG-DOMG), PEG-DSG, and/or PEG-DPG. In some embodiments, the lipid moiety of the PEG-lipids includes those having lengths of from about C14 to about C22, preferably from about C14 to about C16. In some embodiments, a PEG moiety, for example an mPEG-NH2, has a size of about 1000, 2000, 5000, 10,000, 15,000 or 20,000 daltons. In some embodiments, the PEG-lipid is PEG 2k -DMG. In some embodiments, the lipid nanoparticles described herein can comprise a PEG lipid which is a non-diffusible PEG. Non-limiting examples of non-diffusible PEGs include PEG-DSG and PEG-DSPE. PEG-lipids are known in the art, such as those described in U.S. Patent No. 8158601 and International Publ. No. WO 2015/130584 A2, which are incorporated herein by reference in their entirety. In general, some of the other lipid components (e.g., PEG lipids) of various formulae described herein may be synthesized as described International Patent Application No. PCT/US2016/000129, filed December 10, 2016, entitled “Compositions and Methods for Delivery of Therapeutic Agents,” which is incorporated by reference in its entirety. The lipid component of a lipid nanoparticle composition may include one or more molecules comprising polyethylene glycol, such as PEG or PEG-modified lipids. Such species may be alternately referred to as PEGylated lipids. A PEG lipid is a lipid modified with polyethylene glycol. A PEG lipid may be selected from the non-limiting group including PEG- modified phosphatidylethanolamines, PEG-modified phosphatidic acids, PEG-modified ceramides, PEG-modified dialkylamines, PEG-modified diacylglycerols, PEG-modified dialkylglycerols, and mixtures thereof. For example, a PEG lipid may be PEG-c-DOMG, PEG- DMG, PEG-DLPE, PEG-DMPE, PEG-DPPC, or a PEG-DSPE lipid. In some embodiments the PEG-modified lipids are a modified form of PEG DMG. PEG- DMG has the following structure: In some embodiments, PEG lipids useful in the present invention can be PEGylated lipids described in International Publication No. WO2012099755, the contents of which is herein incorporated by reference in its entirety. Any of these exemplary PEG lipids described herein may be modified to comprise a hydroxyl group on the PEG chain. In certain embodiments, the PEG lipid is a PEG-OH lipid. As generally defined herein, a “PEG-OH lipid” (also referred to herein as “hydroxy-PEGylated lipid”) is a PEGylated lipid having one or more hydroxyl (–OH) groups on the lipid. In certain embodiments, the PEG-OH lipid includes one or more hydroxyl groups on the PEG chain. In certain embodiments, a PEG-OH or hydroxy-PEGylated lipid comprises an –OH group at the terminus of the PEG chain. Each possibility represents a separate embodiment of the present invention. In certain embodiments, a PEG lipid useful in the present invention is a compound of Formula (X): (X), or salts thereof, wherein: R 3 is –OR O ; R O is hydrogen, optionally substituted alkyl, or an oxygen protecting group; r is an integer between 1 and 100, inclusive; L 1 is optionally substituted C 1-10 alkylene, wherein at least one methylene of the optionally substituted C1-10 alkylene is independently replaced with optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, optionally substituted heteroarylene, O, N(R N ), S, C(O), C(O)N(R N ), NR N C(O), C(O)O, OC(O), OC(O)O, OC(O)N(R N ), NR N C(O)O, or NR N C(O)N(R N ); D is a moiety obtained by click chemistry or a moiety cleavable under physiological conditions; m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; A is of the formula: each instance of L 2 is independently a bond or optionally substituted C1-6 alkylene, wherein one methylene unit of the optionally substituted C 1-6 alkylene is optionally replaced with O, N(R N ), S, C(O), C(O)N(R N ), NR N C(O), C(O)O, OC(O), OC(O)O, OC(O)N(R N ), NR N C(O)O, or NR N C(O)N(R N ); each instance of R 2 is independently optionally substituted C 1-30 alkyl, optionally substituted C 1-30 alkenyl, or optionally substituted C 1-30 alkynyl; optionally wherein one or more methylene units of R 2 are independently replaced with optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, optionally substituted heteroarylene, N(R N ), O, S, C(O), C(O)N(R N ), NR N C(O), NR N C(O)N(R N ), C(O)O, OC(O), - OC(O)O, OC(O)N(R N ), NR N C(O)O, C(O)S, SC(O), C(=NR N ), C(=NR N )N(R N ), NR N C(=NR N ), NR N C(=NR N )N(R N ), C(S), C(S)N(R N ), NR N C(S), NR N C(S)N(R N ), S(O) , OS(O), S(O)O, - OS(O)O, OS(O) 2 , S(O) 2 O, OS(O) 2 O, N(R N )S(O), S(O)N(R N ), N(R N )S(O)N(R N ), OS(O)N(R N ), N(R N )S(O)O, S(O) 2 , N(R N )S(O) 2 , S(O) 2 N(R N ), N(R N )S(O) 2 N(R N ), OS(O) 2 N(R N ), or - N(R N )S(O) 2 O; each instance of R N is independently hydrogen, optionally substituted alkyl, or a nitrogen protecting group; Ring B is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; and p is 1 or 2. In certain embodiments, the compound of Formula (X) is a PEG-OH lipid (i.e., R 3 is – OR O , and R O is hydrogen). In certain embodiments, the compound of Formula (X) is of Formula (X-OH): (X-OH), or a salt thereof. In certain embodiments, a PEG lipid useful in the present invention is a PEGylated fatty acid. In certain embodiments, a PEG lipid useful in the present invention is a compound of Formula (XI). Provided herein are compounds of Formula (XI): , or a salts thereof, wherein: R 3 is–OR O ; R O is hydrogen, optionally substituted alkyl or an oxygen protecting group; r is an integer between 1 and 100, inclusive; R 5 is optionally substituted C10-40 alkyl, optionally substituted C10-40 alkenyl, or optionally substituted C 10-40 alkynyl; and optionally one or more methylene groups of R 5 are replaced with optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, optionally substituted heteroarylene, N(R N ), O, S, C(O), C(O)N(R N ), - NR N C(O), NR N C(O)N(R N ), C(O)O, OC(O), OC(O)O, OC(O)N(R N ), NR N C(O)O, C(O)S, SC(O), C(=NR N ), C(=NR N )N(R N ), NR N C(=NR N ), NR N C(=NR N )N(R N ), C(S), C(S)N(R N ), NR N C(S), - NR N C(S)N(R N ), S(O), OS(O), S(O)O, OS(O)O, OS(O) 2 , S(O) 2 O, OS(O) 2 O, N(R N )S(O), - S(O)N(R N ), N(R N )S(O)N(R N ), OS(O)N(R N ), N(R N )S(O)O, S(O) 2 , N(R N )S(O) 2 , S(O) 2 N(R N ), - N(R N )S(O) 2 N(R N ), OS(O) 2 N(R N ), or N(R N )S(O) 2 O; and each instance of R N is independently hydrogen, optionally substituted alkyl, or a nitrogen protecting group. In certain embodiments, the compound of Formula (XI) is of Formula (XI-OH): or a salt thereof. In some embodiments, r is 40-50. In yet other embodiments the compound of Formula (XI) is: . or a salt thereof. In some embodiments, the compound of Formula (XI) is . In some embodiments, the lipid composition of the pharmaceutical compositions disclosed herein does not comprise a PEG-lipid. In some embodiments, the PEG-lipids may be one or more of the PEG lipids described in U.S. Application No. US15/674,872. In some embodiments, the lipid nanoparticle comprises a molar ratio of 0.5-15% PEG lipid relative to the other lipid components. For example, the lipid nanoparticle may comprise a molar ratio of 0.5-10%, 0.5-5%, 1-15%, 1-10%, 1-5%, 2-15%, 2-10%, 2-5%, 5-15%, 5-10%, or 10-15% PEG lipid. In some embodiments, the lipid nanoparticle comprises a molar ratio of 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15% PEG- lipid. In some embodiments, the lipid nanoparticle comprises 1-5% PEG-modified lipid, optionally 1-3 mol%, for example 1.5 to 2.5 mol%, 1-2 mol%, 2-3 mol%, 3-4 mol%, or 4-5 mol%. In some embodiments, the lipid nanoparticle comprises 0.5-15 mol% PEG-modified lipid. For example, the lipid nanoparticle may comprise 0.5-10 mol%, 0.5-5 mol%, 1-15 mol%, 1-10 mol%, 1-5 mol%, 2-15 mol%, 2-10 mol%, 2-5 mol%, 5-15 mol%, 5-10 mol%, or 10-15 mol%. In some embodiments, the lipid nanoparticle comprises 0.5 mol%, 1 mol%, 2 mol%, 3 mol%, 4 mol%, 5 mol%, 6 mol%, 7 mol%, 8 mol%, 9 mol%, 10 mol%, 11 mol%, 12 mol%, 13 mol%, 14 mol%, or 15 mol% PEG-modified lipid. In some embodiments, the lipid nanoparticle comprises 20-60 mol% ionizable amino lipid, 5-25 mol% non-cationic lipid, 25-55 mol% sterol, and 0.5-15 mol% PEG-modified lipid. In some embodiments, a LNP of the disclosure comprises an ionizable amino lipid of Compound 1, wherein the non-cationic lipid is DSPC, the structural lipid that is cholesterol, and the PEG lipid is DMG-PEG. In some embodiments, a LNP of the invention comprises an ionizable amino lipid of any of Formula VI, VII or VIIII, a phospholipid comprising DSPC, a structural lipid, and a PEG lipid comprising PEG-DMG. In some embodiments, a LNP of the invention comprises an ionizable amino lipid of any of Formula VI, VII or VIII, a phospholipid comprising DSPC, a structural lipid, and a PEG lipid comprising a compound having Formula XI. In some embodiments, a LNP of the invention comprises an ionizable amino lipid of Formula VI, VII or VIII, a phospholipid comprising a compound having Formula VIII, a structural lipid, and the PEG lipid comprising a compound having Formula X or XI. In some embodiments, a LNP of the invention comprises an ionizable amino lipid of Formula VI, VII or VIII, a phospholipid comprising a compound having Formula IX, a structural lipid, and the PEG lipid comprising a compound having Formula X or XI. In some embodiments, a LNP of the invention comprises an ionizable amino lipid of Formula VI, VII or VIII, a phospholipid having Formula IX, a structural lipid, and a PEG lipid comprising a compound having Formula XI. In some embodiments, the lipid nanoparticle comprises 49 mol% ionizable amino lipid, 10 mol% DSPC, 38.5 mol% cholesterol, and 2.5 mol% DMG-PEG. In some embodiments, the lipid nanoparticle comprises 49 mol% ionizable amino lipid, 11 mol% DSPC, 38.5 mol% cholesterol, and 1.5 mol% DMG-PEG. In some embodiments, the lipid nanoparticle comprises 48 mol% ionizable amino lipid, 11 mol% DSPC, 38.5 mol% cholesterol, and 2.5 mol% DMG-PEG. In some embodiments, a LNP of the invention comprises an N:P ratio of from about 2:1 to about 30:1. In some embodiments, a LNP of the invention comprises an N:P ratio of about 6:1. In some embodiments, a LNP of the invention comprises an N:P ratio of about 3:1, 4:1, or 5:1. In some embodiments, a LNP of the invention comprises a wt/wt ratio of the ionizable amino lipid component to the RNA of from about 10:1 to about 100:1. In some embodiments, a LNP of the invention comprises a wt/wt ratio of the ionizable amino lipid component to the RNA of about 20:1. In some embodiments, a LNP of the invention comprises a wt/wt ratio of the ionizable amino lipid component to the RNA of about 10:1. Some embodiments comprise a composition having one or more LNPs having a diameter of about 150 nm or less, such as about 140 nm, 130 nm, 120 nm, 110 nm, 100 nm, 90 nm, 80 nm, 70 nm, 60 nm, 50 nm, 40 nm, 30 nm, or 20 nm or less. Some embodiments comprise a composition having a mean LNP diameter of about 150 nm or less, such as about 140 nm, 130 nm, 120 nm, 110 nm, 100 nm, 90 nm, 80 nm, 70 nm, 60 nm, 50 nm, 40 nm, 30 nm, or 20 nm or less. In some embodiments, the composition has a mean LNP diameter from about 30nm to about 150nm, or a mean diameter from about 60nm to about 120nm. A LNP may comprise or one or more types of lipids, including but not limited to amino lipids (e.g., ionizable amino lipids), neutral lipids, non-cationic lipids, charged lipids, PEG- modified lipids, phospholipids, structural lipids and sterols. In some embodiments, a LNP may further comprise one or more cargo molecules, including but not limited to nucleic acids (e.g., mRNA, plasmid DNA, DNA or RNA oligonucleotides, siRNA, shRNA, snRNA, snoRNA, lncRNA, etc.), small molecules, proteins and peptides. In some embodiments, the composition comprises a liposome. A liposome is a lipid particle comprising lipids arranged into one or more concentric lipid bilayers around a central region. The central region of a liposome may comprise an aqueous solution, suspension, or other aqueous composition. In some embodiments, a lipid nanoparticle may comprise two or more components (e.g., amino lipid and nucleic acid, PEG-lipid, phospholipid, structural lipid). For instance, a lipid nanoparticle may comprise an amino lipid and a nucleic acid. Compositions comprising the lipid nanoparticles, such as those described herein, may be used for a wide variety of applications, including the stealth delivery of therapeutic payloads with minimal adverse innate immune response. Effective in vivo delivery of nucleic acids represents a continuing medical challenge. Exogenous nucleic acids (i.e., originating from outside of a cell or organism) are readily degraded in the body, e.g., by the immune system. Accordingly, effective delivery of nucleic acids to cells often requires the use of a particulate carrier (e.g., lipid nanoparticles). The particulate carrier should be formulated to have minimal particle aggregation, be relatively stable prior to intracellular delivery, effectively deliver nucleic acids intracellularly, and illicit no or minimal immune response. To achieve minimal particle aggregation and pre-delivery stability, many conventional particulate carriers have relied on the presence and/or concentration of certain components (e.g., PEG-lipid). However, it has been discovered that certain components may decrease the stability of encapsulated nucleic acids (e.g., mRNA molecules). The reduced stability may limit the broad applicability of the particulate carriers. As such, there remains a need for methods by which to improve the stability of nucleic acid (e.g., mRNA) encapsulated within lipid nanoparticles. In some embodiments, the lipid nanoparticles comprise one or more of ionizable molecules, polynucleotides, and optional components, such as structural lipids, sterols, neutral lipids, phospholipids and a molecule capable of reducing particle aggregation (e.g., polyethylene glycol (PEG), PEG-modified lipid), such as those described above. In some embodiments, a LNP described herein may include one or more ionizable molecules (e.g., amino lipids or ionizable lipids). The ionizable molecule may comprise a charged group and may have a certain pKa. In certain embodiments, the pKa of the ionizable molecule may be greater than or equal to about 6, greater than or equal to about 6.2, greater than or equal to about 6.5, greater than or equal to about 6.8, greater than or equal to about 7, greater than or equal to about 7.2, greater than or equal to about 7.5, greater than or equal to about 7.8, greater than or equal to about 8. In some embodiments, the pKa of the ionizable molecule may be less than or equal to about 10, less than or equal to about 9.8, less than or equal to about 9.5, less than or equal to about 9.2, less than or equal to about 9.0, less than or equal to about 8.8, or less than or equal to about 8.5. Combinations of the above referenced ranges are also possible (e.g., greater than or equal to 6 and less than or equal to about 8.5). Other ranges are also possible. In embodiments in which more than one type of ionizable molecule are present in a particle, each type of ionizable molecule may independently have a pKa in one or more of the ranges described above. In general, an ionizable molecule comprises one or more charged groups. In some embodiments, an ionizable molecule may be positively charged or negatively charged. For instance, an ionizable molecule may be positively charged. For example, an ionizable molecule may comprise an amine group. As used herein, the term “ionizable molecule” has its ordinary meaning in the art and may refer to a molecule or matrix comprising one or more charged moiety. As used herein, a “charged moiety” is a chemical moiety that carries a formal electronic charge, e.g., monovalent (+1, or -1), divalent (+2, or -2), trivalent (+3, or -3), etc. The charged moiety may be anionic (i.e., negatively charged) or cationic (i.e., positively charged). Examples of positively-charged moieties include amine groups (e.g., primary, secondary, and/or tertiary amines), ammonium groups, pyridinium group, guanidine groups, and imidizolium groups. In a particular embodiment, the charged moieties comprise amine groups. Examples of negatively- charged groups or precursors thereof, include carboxylate groups, sulfonate groups, sulfate groups, phosphonate groups, phosphate groups, hydroxyl groups, and the like. The charge of the charged moiety may vary, in some cases, with the environmental conditions, for example, changes in pH may alter the charge of the moiety, and/or cause the moiety to become charged or uncharged. In general, the charge density of the molecule and/or matrix may be selected as desired. In some cases, an ionizable molecule (e.g., an amino lipid or ionizable lipid) may include one or more precursor moieties that can be converted to charged moieties. For instance, the ionizable molecule may include a neutral moiety that can be hydrolyzed to form a charged moiety, such as those described above. As a non-limiting specific example, the molecule or matrix may include an amide, which can be hydrolyzed to form an amine, respectively. Those of ordinary skill in the art will be able to determine whether a given chemical moiety carries a formal electronic charge (for example, by inspection, pH titration, ionic conductivity measurements, etc.), and/or whether a given chemical moiety can be reacted (e.g., hydrolyzed) to form a chemical moiety that carries a formal electronic charge. The ionizable molecule (e.g., amino lipid or ionizable lipid) may have any suitable molecular weight. In certain embodiments, the molecular weight of an ionizable molecule is less than or equal to about 2,500 g/mol, less than or equal to about 2,000 g/mol, less than or equal to about 1,500 g/mol, less than or equal to about 1,250 g/mol, less than or equal to about 1,000 g/mol, less than or equal to about 900 g/mol, less than or equal to about 800 g/mol, less than or equal to about 700 g/mol, less than or equal to about 600 g/mol, less than or equal to about 500 g/mol, less than or equal to about 400 g/mol, less than or equal to about 300 g/mol, less than or equal to about 200 g/mol, or less than or equal to about 100 g/mol. In some instances, the molecular weight of an ionizable molecule is greater than or equal to about 100 g/mol, greater than or equal to about 200 g/mol, greater than or equal to about 300 g/mol, greater than or equal to about 400 g/mol, greater than or equal to about 500 g/mol, greater than or equal to about 600 g/mol, greater than or equal to about 700 g/mol, greater than or equal to about 1000 g/mol, greater than or equal to about 1,250 g/mol, greater than or equal to about 1,500 g/mol, greater than or equal to about 1,750 g/mol, greater than or equal to about 2,000 g/mol, or greater than or equal to about 2,250 g/mol. Combinations of the above ranges (e.g., at least about 200 g/mol and less than or equal to about 2,500 g/mol) are also possible. In embodiments in which more than one type of ionizable molecules are present in a particle, each type of ionizable molecule may independently have a molecular weight in one or more of the ranges described above. In some embodiments, the percentage (e.g., by weight, or by mole) of a single type of ionizable molecule (e.g., amino lipid or ionizable lipid) and/or of all the ionizable molecules within a particle may be greater than or equal to about 15%, greater than or equal to about 16%, greater than or equal to about 17%, greater than or equal to about 18%, greater than or equal to about 19%, greater than or equal to about 20%, greater than or equal to about 21%, greater than or equal to about 22%, greater than or equal to about 23%, greater than or equal to about 24%, greater than or equal to about 25%, greater than or equal to about 30%, greater than or equal to about 35%, greater than or equal to about 40%, greater than or equal to about 42%, greater than or equal to about 45%, greater than or equal to about 48%, greater than or equal to about 50%, greater than or equal to about 52%, greater than or equal to about 55%, greater than or equal to about 58%, greater than or equal to about 60%, greater than or equal to about 62%, greater than or equal to about 65%, or greater than or equal to about 68%. In some instances, the percentage (e.g., by weight, or by mole) may be less than or equal to about 70%, less than or equal to about 68%, less than or equal to about 65%, less than or equal to about 62%, less than or equal to about 60%, less than or equal to about 58%, less than or equal to about 55%, less than or equal to about 52%, less than or equal to about 50%, or less than or equal to about 48%. Combinations of the above referenced ranges are also possible (e.g., greater than or equal to 20% and less than or equal to about 60%, greater than or equal to 40% and less than or equal to about 55%, etc.). In embodiments in which more than one type of ionizable molecule is present in a particle, each type of ionizable molecule may independently have a percentage (e.g., by weight, or by mole) in one or more of the ranges described above. The percentage (e.g., by weight, or by mole) may be determined by extracting the ionizable molecule(s) from the dried particles using, e.g., organic solvents, and measuring the quantity of the agent using high pressure liquid chromatography (i.e., HPLC), liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), or mass spectrometry (MS). Those of ordinary skill in the art would be knowledgeable of techniques to determine the quantity of a component using the above-referenced techniques. For example, HPLC may be used to quantify the amount of a component, by, e.g., comparing the area under the curve of a HPLC chromatogram to a standard curve. It should be understood that the terms “charged” or “charged moiety” does not refer to a “partial negative charge" or “partial positive charge" on a molecule. The terms “partial negative charge" and “partial positive charge" are given their ordinary meaning in the art. A “partial negative charge" may result when a functional group comprises a bond that becomes polarized such that electron density is pulled toward one atom of the bond, creating a partial negative charge on the atom. Those of ordinary skill in the art will, in general, recognize bonds that can become polarized in this way. According to the disclosures herein, a lipid composition may comprise one or more lipids as described herein. Such lipids may include those useful in the preparation of lipid nanoparticle formulations as described above or as known in the art. The term "pure" as used herein refers to material that has only the target nucleic acid active agents such that the presence of unrelated nucleic acids is reduced or eliminated, i.e., impurities or contaminants, including RNA fragments, double stranded RNA, and reverse complement impurities. For example, a purified RNA sample includes one or more target or test nucleic acids but is preferably substantially free of other nucleic acids detectable by methods described herein. As used herein, the term "substantially free" is used operationally, in the context of analytical testing of the material. Preferably, purified material is substantially free of one or more impurities or contaminants including the reverse complement transcription products and/or cytokine-inducing RNA contaminant described herein and for instance is at least 50%, 55%, 60%, 63%, 65%, 70%, 75%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, or 97% pure; more preferably, at least 98% pure, and more preferably still at least 99% pure. In some embodiments a pure RNA (e.g., mRNA) sample is comprised of 100% of the target or test RNAs and includes no other RNA. In certain embodiments, the nucleic acid (e.g., mRNA) is not self- replicating RNA. As used herein, the term “intact” refers to material (e.g., RNA, such as mRNA) that is full length (i.e., does not include fragments). In some embodiments, the intact material (e.g., RNA, such as mRNA) is pure RNA. The purity of a composition may be characterized based on the presence of impurities in the composition at any particular point in time. Impurities include, for instance, lipid-RNA adducts, which are typical degradation products of mRNA-LNPs or elemental metals. In some embodiments, a composition is considered to have an adequate purity if less than 10% of the RNA in a composition is in the form of a lipid-RNA adduct. In some embodiments, a composition is considered to have an adequate purity if less than 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1% of the RNA in a composition is in the form of a lipid-RNA adduct. According to the present disclosure, the term “elemental metal” is given its ordinary meaning in the art. A metal is an element that readily forms positive ions (i.e., cations) and forms metallic bonds. An elemental metal refers to a metal which is not present in a salt form or otherwise within a compound. Those of ordinary skill in the art will, in general, recognize elemental metals. Purity can be determined by any suitable method known in the art. Non-limiting examples of methods to determine the purity of a compound include melting point determination, boiling point determination, spectroscopy (e.g., UV-VIS spectroscopy), titration, chromatography (e.g., liquid chromatography or gas chromatography, such as anion exchange chromatography, high performance liquid chromatography (HPLC), or reversed-phase ultra high- performance liquid chromatography (RP-UHPLC)), mass spectrometry, capillary electrophoresis, and optical rotation. In some embodiments, the percentage of intact RNA is determined by performing HPLC or RP-UHPLC and integrating the area under the curve (AUC) of all RNA peaks (including products shorter than the full-length product and the full-length product) and taking the main peak (representative of full length RNA) as an area percent of the total peak area. According to some embodiments, compositions (e.g., liquid pharmaceutical compositions) disclosed herein are formulated in aqueous solutions. An aqueous solution is a solution in which components are dissolved or otherwise dispersed within water or an aqueous buffer solution. In some embodiments, an aqueous solution disclosed herein has a given pH value. In some embodiments, the pH of an aqueous solution disclosed herein is within the range of about 4.5 to about 8.5. In some embodiments, the pH of an aqueous solution is within the range of about 5 to about 8, about 6 to about 8, about 7 to about 8, about 6.5 to about 8, about 6.5 to about 7.5, about 6.5 to about 7, about 7.5 to about 8.5, or any range or combination thereof. In some embodiments, the pH of an aqueous solution is or is about 5, is or is about 5.5, is or is about 6, is or is about 6.5, is or is about 7, is or is about 7.4, is or is about 7.5, or is or is about 8. In some embodiments, an aqueous solution disclosed herein comprises a pH buffer component, such as a phosphate buffer, a tris buffer, an acetate buffer, a histidine buffer or a citrate buffer, among others. Such a buffer acts to modulate the pH of an aqueous solution, such as an aqueous solution having a pH of 5, 5.5, 6, 6.5, 7, 7.4, 7.5 or 8. Aqueous solutions may comprise various concentrations of salts (e.g., buffer salts, sucrose, NaCl, etc.). In some embodiments, an aqueous solution may comprise a salt (e.g., NaCl) in a concentration of or about 50 mM, of or about 60 mM, of or about 70 mM, of or about 80 mM, of or about 90 mM, of or about 100 mM, of or about 110 mM, of or about 120 mM, of or about 130 mM, of or about 140 mM, of or about 150 mM, of or about 160 mM, of or about 170 mM, of or about 180 mM, of or about 190 mM, of or about 200 mM, or any intermediate concentration therein. In embodiments in which an aqueous solution comprises more than one salt, each salt may independently have a concentration of one or more of the values described above. In some embodiments, the article comprises a container. In certain cases, the container houses the liquid pharmaceutical composition. In some embodiments, the article and/or the container comprises a vial, a syringe, a cartridge, an infusion pump, and/or a light protective container. In certain embodiments, the article and/or the container comprises a label (e.g., a label on the container). In accordance with certain embodiments, the label identifies a number of individual doses of the liquid pharmaceutical composition housed in the container, an amount of each individual dose of the liquid pharmaceutical composition to be administered to a subject, and/or an effective dose of RNA within the liquid pharmaceutical composition within each individual dose. In some instances, the label indicates appropriate storage conditions for the article and/or container. For example, in some cases, the label indicates that the article should not be stored at the glass transition temperature of the composition (e.g., liquid pharmaceutical composition). Without wishing to be bound by theory, it is believed that the stability of the RNA (e.g., mRNA) is lowest at the glass transition temperature. As used herein, the glass transition temperature is the temperature at which an amorphous substance transitions from a hard and relatively brittle (“glassy”) state into a rubbery or viscous state. In some embodiments, the glass transition temperature of the composition is greater than or equal to -50 °C, greater than or equal to -45 °C, greater than or equal to -40 °C, or greater than or equal to -35 °C. In certain cases, the glass transition temperature of the composition is less than or equal to -20 °C, less than or equal to -25 °C, less than or equal to -30 °C, less than or equal to -35 °C, or less than or equal to -40 °C. Combinations of these ranges are also possible (e.g., greater than or equal to -50 °C and less than or equal to -20 °C, greater than or equal to -45 °C and less than or equal to -30 °C, or greater than or equal to -35 °C and less than or equal to -30 °C). In certain embodiments, the label indicates that the article should not be stored at a particular temperature. For example, in some instances, the label indicates that the article should not be stored at a temperature of greater than or equal to -70 °C, greater than or equal to -50 °C, greater than or equal to -45 °C, greater than or equal to -40 °C, or greater than or equal to -35 °C. In certain cases, the label indicates that the article should not be stored at a temperature of less than or equal to -20 °C, less than or equal to -25 °C, less than or equal to -30 °C, less than or equal to -35 °C, or less than or equal to -40 °C. Combinations of these ranges are also possible (e.g., greater than or equal to -50 °C and less than or equal to -20 °C, greater than or equal to -45 °C and less than or equal to -30 °C, greater than or equal to -35 °C and less than or equal to -30 °C, or greater than or equal to -40 °C and less than or equal to -20 °C). According to some embodiments, the label suggests an amount of the liquid pharmaceutical composition to be administered to a subject. In certain embodiments, the amount is greater than or equal to (1 + the fraction of the RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the liquid pharmaceutical composition). For example, if the shelf-life of the article were 3 months at 5 °C, and if 10% (or 0.1) of the RNA in the liquid pharmaceutical composition would degrade after 3 months stored at 5 °C, then the amount is greater than or equal to (1 + 0.1) x (an individual dose of the liquid pharmaceutical composition). For example, if the individual dose of the liquid pharmaceutical composition was 100 micrograms, then the amount would be greater than or equal to 110 micrograms. In some embodiments, the amount is greater than or equal to (1 + the fraction of the RNA that would have degraded in the liquid pharmaceutical composition at the time of administration) x (an individual dose of the liquid pharmaceutical composition). For example, if the RNA in the liquid pharmaceutical composition degrades at a rate of 10% (or 0.1) per month at 5 °C, then the label would suggest administering greater than or equal to (1+0.1) x (an individual dose of the liquid pharmaceutical composition) after 1 month of storage at 5 °C, greater than or equal to (1+0.2) x (an individual dose of the liquid pharmaceutical composition) after 2 months of storage at 5 °C, and/or greater than or equal to (1+0.3) x (an individual dose of the liquid pharmaceutical composition) after 3 months of storage at 5 °C. The fraction of the RNA (e.g., mRNA) that would degrade in the liquid pharmaceutical composition (e.g., over the shelf-life of the article or by the time of administration) is determined by the rate of decay (wherein the rate of decay is degradation over time) of the RNA (e.g., mRNA) in given conditions (e.g., at a particular temperature, such as 5 °C) and the amount of time. The rate of decay and/or the fraction of the RNA (e.g., mRNA) that degrades may be measured as a decrease in purity over time (e.g., an increase in mRNA fragments or a decrease in intact mRNA). Purity may be measured by reverse phase HPLC. In some embodiments, the degradation follows first order kinetics. For example, in certain cases, degradation follows the following equation: ^ ^ ^ ^ = ^ ^ 0 ^ ^ ^^^ where P(0) is percent mRNA purity at time 0, t is the number of months after time 0, P(t) is the percent mRNA purity at time t, and k is the fraction of the mRNA that would degrade in one month in the given conditions. For example, if 1.7% of the mRNA would degrade in 1 month at the given conditions (e.g., at 5 °C) then k would be 0.017. If the purity were 100% at time 0 (so P(0) is 100%) and the product would no longer be effective if the purity of the mRNA dropped below 50% (P(t) is 50%), then the amount of time that the product could be kept in those conditions (e.g., 5 °C) and still be effective could be determined as follows: t = ln (50%/100%) / -0.027 = 40 months. In cases where P(0) is not 100%, P(0) may artificially be set as 100% and P(t) may be normalized accordingly. In certain embodiments, the rate of decay of the RNA (e.g., mRNA) at a given temperature (e.g., any temperature disclosed herein) (e.g., -70 ℃, -40 ℃, -20 ℃, 5 °C, and/or 25 ℃) is greater than or equal to 0.1%/month, greater than or equal to 0.5%/month, greater than or equal to 1%/month, greater than or equal to 3%/month, greater than or equal to 5%/month, greater than or equal to 7%/month, greater than or equal to 8%/month, greater than or equal to 9%/month, greater than or equal to 10%/month, greater than or equal to 12%/month, greater than or equal to 20%/month, greater than or equal to 30%/month, greater than or equal to 40%/month, or greater than or equal to 50%/month. In some embodiments, the rate of decay of the RNA (e.g., mRNA) at a given temperature (e.g., any temperature disclosed herein) (e.g., -70 ℃, -40 ℃, -20 ℃, 5 °C, and/or 25 ℃) is less than or equal to 60%/month, less than or equal to 50%/month, less than or equal to 40%/month, less than or equal to 30%/month, less than or equal to 20%/month, less than or equal to 15%/month, less than or equal to 12%/month, less than or equal to 11%/month, less than or equal to 10%/month, less than or equal to 9%/month, less than or equal to 8%/month, less than or equal to 5%/month, less than or equal to 3%/month, less than or equal to 2%/month, or less than or equal to 1%/month. Combinations of these ranges are also possible (e.g., greater than or equal to 0.1%/month and less than or equal to 60%/month, greater than or equal to 1%/month and less than or equal to 15%/month, greater than or equal to 7%/month and less than or equal to 11%/month, or greater than or equal to 8%/month and less than or equal to 10%/month). For example, in some cases, the rate of decay of the RNA at -70 ℃ and/or -40 ℃ is greater than or equal to 0.1%/month and less than or equal to 5%/month or greater than or equal to 0.1%/month and less than or equal to 1%/month. As another example, in certain instances, the rate of decay of the RNA at -20 ℃ is greater than or equal to 0.1%/month and less than or equal to 8%/month, greater than or equal to 0.5%/month and less than or equal to 5%/month, or greater than or equal to 1%/month and less than or equal to 3%/month. As yet another example, in some instances, the rate of decay of the RNA at 25 ℃ is greater than or equal to 10%/month and less than or equal to 60%/month, greater than or equal to 30%/month and less than or equal to 60%/month, or greater than or equal to 50%/month and less than or equal to 60%/month). In certain embodiments, the rate of decay of the RNA (e.g., mRNA) at greater than or equal to 0 ℃ and less than or equal to 10 ℃ (e.g., 5 °C) is greater than or equal to 1%/month, greater than or equal to 3%/month, greater than or equal to 5%/month, greater than or equal to 7%/month, greater than or equal to 8%/month, greater than or equal to 9%/month, greater than or equal to 10%/month, or greater than or equal to 12%/month. In some embodiments, the rate of decay of the RNA (e.g., mRNA) at greater than or equal to 0 ℃ and less than or equal to 10 ℃ (e.g., 5 °C) is less than or equal to 15%/month, less than or equal to 12%/month, less than or equal to 11%/month, less than or equal to 10%/month, less than or equal to 9%/month, less than or equal to 8%/month, less than or equal to 5%/month, or less than or equal to 3%/month. Combinations of these ranges are also possible (e.g., greater than or equal to 1%/month and less than or equal to 15%/month, greater than or equal to 7%/month and less than or equal to 11%/month, or greater than or equal to 8%/month and less than or equal to 10%/month). In some embodiments, the amount is greater than or equal to 1.05 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.07 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.08 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.10 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.15 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.25 x (an individual dose of the liquid pharmaceutical composition), or greater than or equal to 1.3 x (an individual dose of the liquid pharmaceutical composition). In certain embodiments, the amount is less than or equal to 2.00 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.8 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.6 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.4 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.3 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.25 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition), or less than or equal to 1.1 x (an individual dose of the liquid pharmaceutical composition). Combinations of these ranges are also possible (e.g., greater than or equal to 1.05 x (an individual dose of the liquid pharmaceutical composition) and less than or equal to 2.00 x (an individual dose of the liquid pharmaceutical composition) or greater than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition) and less than or equal to 1.3 x (an individual dose of the liquid pharmaceutical composition)). In accordance with certain embodiments, the container comprises a total amount of RNA (e.g., mRNA). In some cases, the total amount of RNA (e.g., mRNA) comprises greater than or equal to 40%, greater than or equal to 45%, greater than or equal to 50%, greater than or equal to 55%, greater than or equal to 60%, greater than or equal to 65%, greater than or equal to 70%, greater than or equal to 75%, greater than or equal to 80%, greater than or equal to 85%, greater than or equal to 90%, or greater than or equal to 95% intact RNA (e.g., when administered to a subject, at the time of expiration, after storage, and/or at the end of its shelf-life). In certain instances, the total amount of RNA (e.g., mRNA) comprises less than or equal to 95%, less than or equal to 90%, less than or equal to 85%, less than or equal to 80%, less than or equal to 75%, less than or equal to 70%, less than or equal to 65%, less than or equal to 60%, less than or equal to 55%, or less than or equal to 50% intact RNA (e.g., when administered to a subject, at the time of expiration, after storage, and/or at the end of its shelf-life). Combinations of these ranges are also possible (e.g., greater than or equal to 40% and less than or equal to 95%, greater than or equal to 40% and less than or equal to 80%, greater than or equal to 40% and less than or equal to 70%, greater than or equal to 70% and less than or equal to 95%, greater than or equal to 75% and less than or equal to 90%, or greater than or equal to 75% and less than or equal to 80%). In certain cases, the percentage of intact RNA (e.g., mRNA) (e.g., in the container) comprises the percentage of intact RNA that would degrade in the liquid pharmaceutical composition over a shelf-life of the article + greater than or equal to 15%, greater than or equal to 20%, greater than or equal to 25%, greater than or equal to 30%, greater than or equal to 35%, greater than or equal to 40%, greater than or equal to 45%, greater than or equal to 50%, greater than or equal to 55%, greater than or equal to 60%, greater than or equal to 65%, greater than or equal to 70%, or greater than or equal to 75% of the total RNA. In some instances, the percentage of intact RNA (e.g., mRNA) (e.g., in the container) comprises the percentage of intact RNA that would degrade in the liquid pharmaceutical composition over a shelf-life of the article + less than or equal to 80%, less than or equal to 75%, less than or equal to 70%, less than or equal to 65%, less than or equal to 60%, less than or equal to 55%, less than or equal to 50%, less than or equal to 45%, or less than or equal to 40% of the total RNA. Combinations of these ranges are also possible (e.g., the percentage of intact RNA that would degrade in the liquid pharmaceutical composition over a shelf-life of the article + greater than or equal to 15% and less than or equal to 80% of the total RNA, the percentage of intact RNA that would degrade in the liquid pharmaceutical composition over a shelf-life of the article + greater than or equal to 25% and less than or equal to 70%, or the percentage of intact RNA that would degrade in the liquid pharmaceutical composition over a shelf-life of the article + greater than or equal to 40% and less than or equal to 60%). In some embodiments, the total amount of RNA (e.g., mRNA) comprises greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, greater than or equal to 20%, greater than or equal to 25%, greater than or equal to 30%, greater than or equal to 35%, greater than or equal to 40%, greater than or equal to 45%, greater than or equal to 50%, or greater than or equal to 55% RNA that is less than full length RNA (e.g., fragmented RNA) (e.g., when administered to a subject, at the time of expiration, after storage, and/or at the end of its shelf-life). In certain embodiments, the total amount of RNA (e.g., mRNA) comprises less than or equal to 60%, less than or equal to 55%, less than or equal to 50%, less than or equal to 45%, less than or equal to 40%, less than or equal to 35%, less than or equal to 30%, less than or equal to 25%, less than or equal to 20%, less than or equal to 15%, or less than or equal to 10% RNA that is less than full length RNA (e.g., fragmented RNA) (e.g., when administered to a subject, at the time of expiration, after storage, and/or at the end of its shelf-life). Combinations of these ranges are also possible (e.g., greater than or equal to 5% and less than or equal to 60%, greater than or equal to 20% and less than or equal to 60%, greater than or equal to 30% and less than or equal to 60%, greater than or equal to 5% and less than or equal to 30%, or greater than or equal to 20% and less than or equal to 25%). According to certain embodiments, the total amount of RNA (e.g., mRNA) in the container has a value of at least the number of individual doses in the container times 5% greater (e.g., at least 10% greater, 15% greater, 20% greater, 25% greater, 30% greater, 35% greater, 40% greater, 45% greater, or 50% greater) than the amount of the effective dose of RNA within each individual dose. In some embodiments, the total amount of RNA (e.g., mRNA) in the container has a value of less than or equal to the number of individual doses in the container times 100% greater (e.g., less than or equal to 80% greater, 60% greater, 50% greater, 40% greater, 30% greater, 25% greater, 20% greater, or 10% greater) than the amount of the effective dose of RNA within each individual dose. Combinations of these ranges are also possible (e.g., at least the number of individual doses in the container times 5% greater than the amount of the effective dose of RNA within each individual dose and less than or equal to the number of individual doses in the container times 100% greater than the amount of the effective dose of RNA within each individual dose, at least the number of individual doses in the container times 20% greater than the amount of the effective dose of RNA within each individual dose and less than or equal to the number of individual doses in the container times 50% greater than the amount of the effective dose of RNA within each individual dose). For example, if the total amount of RNA in the container has a value of at least the number of individual doses in the container times 5% greater than the amount of the effective dose of RNA within each individual dose, the container has 10 individual doses, and each dose is 100 micrograms of RNA, then the container would have at least (1.05 * 10 * 100) 1,050 micrograms. In some embodiments, an individual dose is the individual dose needed to produce a therapeutically effective amount of a protein in the subject. In certain instances, the individual dose of the liquid pharmaceutical composition is the individual dose of the liquid pharmaceutical composition needed at the time of manufacturing to produce a therapeutically effective amount of a protein in the subject. In certain cases, an individual dose is the individual dose approved by a regulatory agency (such as the FDA) to stimulate an antigen specific immune response in the subject. In certain embodiments, an effective dose and/or effective amount of RNA (e.g., mRNA) (e.g., intact RNA) is the amount of RNA (e.g., mRNA) (e.g., intact RNA) needed to produce a therapeutically effective amount of a protein in the subject. In certain cases, an effective dose and/or effective amount of RNA (e.g., mRNA) (e.g., intact RNA) is the amount of RNA (e.g., mRNA) (e.g., intact RNA) approved by a regulatory agency (such as the FDA) to stimulate an antigen specific immune response in the subject. As used herein, the term “amount” refers to total mass (e.g., mg). As a person of ordinary skill in the art would understand, the total mass of a component (e.g., RNA) may be adjusted in multiple ways. For example, if an article is comprised of a solution comprising RNA, the total mass of the RNA in the article could be increased in multiple ways, such as adding more of the RNA to the article (e.g., by increasing the concentration of the RNA in the solution) and/or increasing the volume of the solution (e.g., a solution with a constant concentration). Thus, the amount of a liquid pharmaceutical composition is an amount comprising a total mass of RNA. An amount of RNA is a mass of RNA. An amount of intact RNA is a mass of full length RNA. Similarly, as used herein, the term “dose” or “individual dose” refers to total mass (e.g., mg). For example, a dose of full length RNA is 50 mg of full length RNA in some embodiments. As a person of ordinary skill in the art would understand, while a dose may be referred to in units other than mass (e.g., 1 pill, 2 capsules, 1 tube of ointment, 2 drops, 1 mL of solution, etc.), the dose may always be translated into mass. For example, if a dose is 1 mL of a liquid pharmaceutical composition, and the liquid pharmaceutical composition has a density of 10 mg/mL, and the concentration of full length RNA in the liquid pharmaceutical is 1 mg/mL, then the dose of liquid pharmaceutical composition is 10 mg of liquid pharmaceutical composition and the dose of full length RNA is 1 mg. A baseline dose is a dose having a specific mass of RNA prior to storage of a composition. In certain embodiments, an individual dose and/or effective amount is at least 5 micrograms, at least 10 micrograms, at least 20 micrograms, at least 30 micrograms, at least 40 micrograms, at least 50 micrograms, at least 60 micrograms, at least 70 micrograms, at least 80 micrograms, at least 90 micrograms, at least 100 micrograms, at least 125 micrograms, or at least 150 micrograms of intact mRNA. In some embodiments, an individual dose and/or effective amount is less than or equal to 200 micrograms, less than or equal to 175 micrograms, less than or equal to 150 micrograms, less than or equal to 125 micrograms, less than or equal to 100 micrograms, less than or equal to 90 micrograms, less than or equal to 80 micrograms, less than or equal to 70 micrograms, less than or equal to 60 micrograms, less than or equal to 50 micrograms, or less than or equal to 40 micrograms. Combinations of these ranges are also possible (e.g., at least 5 micrograms and less than or equal to 200 micrograms, at least 20 micrograms and less than or equal to 50 micrograms, or at least 40 micrograms and less than or equal to 60 micrograms). In some embodiments, a composition and/or an article (e.g., a container) comprises at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% more intact RNA than an individual dose and/or effective amount of the intact RNA. In certain embodiments, a composition and/or an article (e.g., a container) comprises less than or equal to 200%, less than or equal to 150%, less than or equal to 100%, less than or equal to 90%, less than or equal to 80%, less than or equal to 70%, less than or equal to 60%, less than or equal to 50%, less than or equal to 40%, less than or equal to 30%, or less than or equal to 20% more intact RNA than an individual dose and/or effective amount of the intact RNA. Combinations of these ranges are also possible (e.g., at least 5% and less than or equal to 20, at least 20% and less than or equal to 100%, or at least 20% and less than or equal to 50%). In some embodiments, the article has a particular shelf-life at a particular temperature. As used herein, the shelf-life is the amount of time for which the article can be stored in a particular set of conditions and still be used safely and effectively (e.g., the amount of time for which the article can be stored in a particular set of conditions and still be used according to FDA guidelines). For example, in certain cases, the article has a shelf-life of and/or can be stored (or is stored) for greater than or equal to 1 month, greater than or equal to 2 months, greater than or equal to 3 months, greater than or equal to 6 months, or greater than or equal to 9 months. In some embodiments, the article has a shelf-life of and/or can be stored (or is stored) for less than or equal to 1 year, less than or equal to 9 months, or less than or equal to 6 months. Combinations of these ranges are also possible (e.g., greater than or equal to 3 months and less than or equal to 1 year). In some instances, the shelf-life is determined when stored at a temperature of (and/or the composition and/or article can be stored (or is stored) at a temperature of) greater than 0 °C, greater than or equal to 1 °C, greater than or equal to 2 °C, greater than or equal to 3 °C, greater than or equal to 4 °C, or greater than or equal to 5 °C. In certain embodiments, the shelf-life is determined when stored at a temperature of (and/or the composition and/or article can be stored (or is stored) at a temperature of) less than or equal to 10 °C, less than or equal to 9 °C, less than or equal to 8 °C, less than or equal to 7 °C, less than or equal to 6 °C, or less than or equal to 5 °C. Combinations of these ranges are also possible (e.g., greater than 0 °C and less than or equal to 10 °C, or 5°C). As used herein, the shelf-life is determined at standard pressure and in the absence of any additional components (e.g., contaminations or stabilizers) that do not form part of the article and/or liquid pharmaceutical composition (e.g., do not form part of the article and/or liquid pharmaceutical composition as approved by the FDA). In some embodiments, the shelf-life comprises a first period of time at a first temperature followed by a second period of time at a second temperature. In some instances, the first period of time is greater than the second period of time. In certain embodiments, the second temperature is higher than the first temperature. For example, in some cases, the article (e.g., liquid pharmaceutical composition) may be stored frozen (e.g., at -70 °C) for a period of time (such as greater than or equal to 1 year after it is filled). In some embodiments the first period of time can be at multiple frozen temperatures (e.g., -70°C and then -20°C). In some cases, it may then be transported to a consumer, where it may be stored as a liquid (e.g., at 5 °C) for greater than or equal to 3 months. In certain cases, the first period of time is greater than or equal to 3 months, greater than or equal to 6 months, greater than or equal to 9 months, greater than or equal to 1 year, greater than or equal to 15 months, or greater than or equal to 18 months. In some instances, the first period of time is less than or equal to 2 years, less than or equal to 18 months, less than or equal to 1 year, or less than or equal to 6 months. Combinations of these range are also possible (e.g., greater than or equal to 3 months and less than or equal to 2 years). In some instances, the first temperature is less than or equal to -20 °C, less than or equal to -30 °C, less than or equal to -40 °C, less than or equal to -50 °C, less than or equal to -60 °C, or less than or equal to -70 °C. In certain embodiments, the first temperature is greater than or equal to -90 °C, greater than or equal to -80 °C, greater than or equal to -70 °C, greater than or equal to -60 °C, greater than or equal to -50 °C, greater than or equal to -40 °C, or greater than or equal to -30 °C. Combinations of these ranges are also possible (e.g., less than or equal to -20 °C and greater than or equal to -90 °C, less than or equal to -50 °C and greater than or equal to -90 °C, or -70 °C). In certain embodiments, the second period is greater than or equal to 1 month, greater than or equal to 2 months, greater than or equal to 3 months, greater than or equal to 6 months, or greater than or equal to 9 months. In some embodiments, the second period is less than or equal to 1 year, less than or equal to 9 months, or less than or equal to 6 months. Combinations of these ranges are also possible (e.g., greater than or equal to 3 months and less than or equal to 1 year). In some embodiments, the second temperature is greater than 0 °C, greater than or equal to 1 °C, greater than or equal to 2 °C, greater than or equal to 3 °C, greater than or equal to 4 °C, or greater than or equal to 5 °C. In certain embodiments, the second temperature is less than or equal to 10 °C, less than or equal to 9 °C, less than or equal to 8 °C, less than or equal to 7 °C, less than or equal to 6 °C, or less than or equal to 5 °C. Combinations of these ranges are also possible (e.g., greater than 0 °C and less than or equal to 10 °C, or 5°C). In certain embodiments, a particular percentage of the RNA (e.g., mRNA) is intact at the end of the shelf-life and/or after storage (e.g., after 3 months at 5°C). For example, in certain cases, greater than or equal to 15%, greater than or equal to 18%, greater than or equal to 20%, greater than or equal to 25%, greater than or equal to 30%, greater than or equal to 35%, greater than or equal to 40%, greater than or equal to 45%, greater than or equal to 50%, greater than or equal to 55%, greater than or equal to 60%, greater than or equal to 65%, greater than or equal to 70%, greater than or equal to 75%, greater than or equal to 80%, greater than or equal to 85%, greater than or equal to 90%, or greater than or equal to 95% of the RNA (e.g., mRNA) is intact at the end of the shelf-life and/or after storage. In some instances, less than or equal to 95%, less than or equal to 90%, less than or equal to 85%, less than or equal to 80%, less than or equal to 75%, less than or equal to 70%, less than or equal to 65%, less than or equal to 60%, less than or equal to 55%, less than or equal to 50%, less than or equal to 45%, less than or equal to 40%, less than or equal to 35%, less than or equal to 30%, less than or equal to 25%, or less than or equal to 20% of the RNA (e.g., mRNA) is intact at the end of the shelf-life and/or after storage. Combinations of these ranges are also possible (e.g., greater than or equal to 15% and less than or equal to 95%, greater than or equal to 40% and less than or equal to 95%, greater than or equal to 40% and less than or equal to 80%, greater than or equal to 40% and less than or equal to 70%, greater than or equal to 70% and less than or equal to 95%, greater than or equal to 75% and less than or equal to 90%, or greater than or equal to 75% and less than or equal to 80%). In some embodiments, methods of filling an article (e.g., any article described herein) are described. In certain embodiments, the method comprises adding a nucleic acid (e.g., RNA, such as mRNA) to the article. In some cases, the method comprises adding a lipid carrier (e.g., a lipid nanoparticle, liposome, and/or lipoplex) to the article. In certain instances, the nucleic acid (e.g., mRNA) and lipid carrier (e.g., LNP) may be added separately or in combination (e.g., in the form of a liquid pharmaceutical composition, for example, where the nucleic acid (e.g., mRNA) is formulated in the lipid carrier (e.g., LNP)). In some embodiments, the method comprises freezing the nucleic acid (e.g., mRNA) and/or lipid carrier (e.g., LNP) (individually or in combination as a pharmaceutical composition) prior to addition to the article. According to some embodiments, the addition of the nucleic acid (e.g., mRNA) and/or the lipid carrier (or the liquid pharmaceutical composition) forms an amount of a liquid pharmaceutical composition in the article. According to some embodiments, the amount of the liquid pharmaceutical composition formed in the article is greater than or equal to (1 + the fraction of the RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the liquid pharmaceutical composition). In some embodiments, the amount is greater than or equal to 1.05 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.07 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.08 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.10 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.15 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition), greater than or equal to 1.25 x (an individual dose of the liquid pharmaceutical composition), or greater than or equal to 1.3 x (an individual dose of the liquid pharmaceutical composition). In certain embodiments, the amount is less than or equal to 2.00 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.8 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.6 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.4 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.3 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.25 x (an individual dose of the liquid pharmaceutical composition), less than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition), or less than or equal to 1.1 x (an individual dose of the liquid pharmaceutical composition). Combinations of these ranges are also possible (e.g., greater than or equal to 1.05 x (an individual dose of the liquid pharmaceutical composition) and less than or equal to 2.00 x (an individual dose of the liquid pharmaceutical composition) or greater than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition) and less than or equal to 1.3 x (an individual dose of the liquid pharmaceutical composition)). In accordance with certain embodiments, the method comprises storing the article for a duration of time (e.g., up to 1 year or up to 3 years) at a temperature (e.g., greater than 0 °C and less than 10 °C, or 5 °C). In some instances, the method comprises storing the article for a duration of time up to the shelf-life of the article (e.g., any shelf-life described herein). In certain cases, a particular percentage of the RNA (e.g., mRNA) is intact after the storing step (e.g., a particular percentage of the RNA is intact if stored for the shelf-life of the article). For example, in some instances, greater than or equal to 15%, greater than or equal to 18%, greater than or equal to 20%, greater than or equal to 25%, greater than or equal to 30%, greater than or equal to 35%, greater than or equal to 40%, greater than or equal to 45%, greater than or equal to 50%, greater than or equal to 55%, greater than or equal to 60%, greater than or equal to 65%, greater than or equal to 70%, greater than or equal to 75%, greater than or equal to 80%, greater than or equal to 85%, greater than or equal to 90%, or greater than or equal to 95% of the RNA (e.g., mRNA) is intact after the storing step. In some instances, less than or equal to 95%, less than or equal to 90%, less than or equal to 85%, less than or equal to 80%, less than or equal to 75%, less than or equal to 70%, less than or equal to 65%, less than or equal to 60%, less than or equal to 55%, less than or equal to 50%, less than or equal to 45%, less than or equal to 40%, less than or equal to 35%, less than or equal to 30%, less than or equal to 25%, or less than or equal to 20% of the RNA (e.g., mRNA) is intact after the storing step. Combinations of these ranges are also possible (e.g., greater than or equal to 15% and less than or equal to 95%, greater than or equal to 40% and less than or equal to 95%, greater than or equal to 40% and less than or equal to 80%, greater than or equal to 40% and less than or equal to 70%, greater than or equal to 70% and less than or equal to 95%, greater than or equal to 75% and less than or equal to 90%, or greater than or equal to 75% and less than or equal to 80%). In some embodiments, the percentage of the RNA (e.g., mRNA) that is intact after the storing step is lower than the percentage of the RNA (e.g., mRNA) that is intact prior to the storing step. In certain embodiments, the percentage of the RNA (e.g., mRNA) that is intact prior to the storing step is at least 40%, such as at least 50%, at least 55%, at least 60%, at least 63%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95%. In some cases, the percentage of the RNA (e.g., mRNA) that is intact prior to the storing step is less than or equal to 100%, less than or equal to 99%, less than or equal to 98%, less than or equal to 95%, less than or equal to 90%, less than or equal to 85%, less than or equal to 80%, less than or equal to 75%, less than or equal to 70%, less than or equal to 65%, less than or equal to 3%, less than or equal to 60%, less than or equal to 55%, or less than or equal to 55%. Combinations of these ranges are also possible (e.g., at least 40% and less than or equal to 100%, at least 40% and less than or equal to 90%, or at least 50% and less than or equal to 80%). In certain embodiments, the total amount of intact RNA (e.g., mRNA) prior to storage and/or the total amount of intact RNA (e.g., mRNA) after storage is greater than or equal to an effective amount of intact RNA. In some instances, the storing step does not include storing at the glass transition temperature of the composition (e.g., liquid pharmaceutical composition). In certain embodiments, the storing step does not include storing at a temperature of greater than or equal to -50 °C, greater than or equal to -45 °C, greater than or equal to -40 °C, or greater than or equal to -35 °C. In certain cases, the storing step does not include storing at a temperature of less than or equal to -20 °C, less than or equal to -25 °C, less than or equal to -30 °C, less than or equal to - 35 °C, or less than or equal to -40 °C. Combinations of these ranges are also possible (e.g., greater than or equal to -50 °C and less than or equal to -20 °C, greater than or equal to -45 °C and less than or equal to -30 °C, or greater than or equal to -35 °C and less than or equal to -30 °C). In certain embodiments, the method (e.g., any method disclosed herein) and/or composition and/or article (e.g., any article disclosed herein) mitigates and/or accounts for degradation (e.g., from transesterification) of RNA (e.g., mRNA, such as any mRNA disclosed herein). For example, in some embodiments, the method and/or composition and/or article mitigates and/or accounts for degradation of RNA at certain conditions (e.g., any conditions disclosed herein, such as the shelf-life conditions and/or storage conditions disclosed herein, such as in a refrigerator, such as at 5 ℃). In some cases, the method and/or composition and/or article mitigates and/or accounts for degradation of RNA (e.g., at certain conditions) by ensuring that a sufficient amount of intact RNA is provided at the time of administration and/or throughout the shelf-life of the article. In certain instances, ensuring that a sufficient amount of intact RNA is provided at the time of administration and/or throughout the shelf-life of the article comprises providing a sufficient amount of intact RNA at the time of manufacture and/or sale (e.g., providing a sufficient amount of intact RNA at the time of manufacture and/or sale taking into account the amount of RNA that will degrade until the time of administration and/or throughout the shelf-life). In some embodiments, the total amount of intact RNA prior to storage of the composition for a period of time (e.g., as disclosed elsewhere herein) is calculated to account for degradation of the mRNA (e.g., from transesterification of the mRNA) during the storage of the composition for the period of time and/or to ensure at least an effective amount of intact RNA is present throughout the storage and/or shelf-life (and/or at the time of administration). In some embodiments, methods of delivering an effective dose of a nucleic acid (e.g., RNA, such as mRNA) are described herein. In certain embodiments, the method comprises administering a liquid pharmaceutical composition (e.g., any composition or liquid pharmaceutical composition disclosed herein) to a subject. For example, in accordance with certain embodiments, the liquid pharmaceutical composition comprises a nucleic acid (e.g., any nucleic acid disclosed herein, such as an RNA or mRNA encoding a protein) and a lipid carrier (e.g., any lipid carrier disclosed herein, such as an LNP). In some cases, a total dose of nucleic acid (e.g., RNA, such as mRNA) is administered to the subject that is at least 5% (e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%; less than or equal to 100%, less than or equal to 80%, less than or equal to 60%, less than or equal to 50%, less than or equal to 40%, less than or equal to 30%, less than or equal to 25%, less than or equal to 20%, less than or equal to 15%, or less than or equal to 10%; combinations of these ranges are also possible (e.g., at least 5% and less than or equal to 100% or at least 20% and less than or equal to 50%) greater than an effective dose of the nucleic acid (e.g., mRNA). In some embodiments, a subject to which a composition comprising a nucleic acid (e.g., mRNA) formulated in a lipid (e.g., LNP) is administered is a subject that suffers from or is at risk of suffering from a disease, disorder or condition, including a communicable or non- communicable disease, disorder or condition. As used herein, “treating” a subject can include either therapeutic use or prophylactic use relating to a disease, disorder or condition, and may be used to describe uses for the alleviation of symptoms of a disease, disorder or condition, uses for vaccination against a disease, disorder or condition, and uses for decreasing the contagiousness of a disease, disorder or condition, among other uses. In certain embodiments, the nucleic acid (e.g., RNA, such as mRNA) is an mRNA vaccine designed to achieve particular biologic effects. Exemplary vaccines of the invention feature mRNAs encoding a particular antigen of interest (or an mRNA or mRNAs encoding antigens of interest). In exemplary aspects, the vaccines of the invention feature an mRNA or mRNAs encoding antigen(s) derived from infectious diseases. In certain embodiments, the article comprises a vaccine (e.g., an infectious disease vaccine, such as a human cytomegalovirus vaccine). In some embodiments, the antigen comprises an infectious disease antigen. The antigen of the infectious disease vaccine is a viral antigen. In some embodiments the infectious agent is a human cytomegalovirus (hCMV). In some embodiments, a disease, disorder or condition is caused by or associated with a member of the herpes virus family, human cytomegalovirus (hCMV). In some embodiments, the virus is a human cytomegalovirus (hCMV). In some embodiments, the antigen is a human cytomegalovirus (hCMV) antigen. In some embodiments, the article and/or pharmaceutical composition comprises one or more (e.g., greater than or equal to 1, greater than or equal to 2, greater than or equal to 3, greater than or equal to 4, or greater than or equal to 5; less than or equal to 10, less than or equal to 8, less than or equal to 6, less than or equal to 4, or less than or equal to 2; combinations of these ranges are also possible, such as greater than or equal to 1 and less than or equal to 6) hCMV antigens. In some embodiments, the disease, disorder or condition is a disease or condition caused by or associated with human cytomegalovirus (hCMV). HCMV includes several surface glycoproteins that are involved in viral attachment and entry into different cell types. The pentameric complex (PC), composed of gH/gL/UL128/UL130/UL131A, mediates entry into endothelial cells, epithelial cells, and myeloid cells. HCMV proteins UL128, UL130, and UL131A assemble with gH and gL proteins to form a heterologous pentameric complex, designated gH/gL/UL128-131A, found on the surface of the HCMV. Natural variants and deletion and mutational analyses have implicated proteins of the gH/gL/UL128-131A complex with the ability to infect certain cell types, including for example, endothelial cells, epithelial cells, and leukocytes. HCMV enters cells by fusing its envelope with either the plasma membrane (fibroblasts) or the endosomal membrane (epithelial and endothelial cells). HCMV initiates cell entry by attaching to the cell surface heparan sulfate proteoglycans using envelope glycoprotein M (gM) or gB. This step is followed by interaction with cell surface receptors that trigger entry or initiate intracellular signaling. The entry receptor function is provided by gH/gL glycoprotein complexes. Different gH/gL complexes are known to facilitate entry into different cell types including epithelial cells, endothelial cells, or fibroblasts. For example, while entry into fibroblasts requires gH/gL heterodimer, entry into epithelial and endothelial cells requires the pentameric complex gH/gL/UL128/UL130/ UL131 in addition to gH/gL. Thus, different gH/gL complexes engage distinct entry receptors on epithelial/endothelial cells and fibroblasts. Receptor engagement is followed by membrane fusion, a process mediated by gB and gH/ gL. Early antibody studies have supported critical roles for both gB and gH/gL in hCMV entry. gB is essential for entry and cell spread. gB and gH/gL are necessary and sufficient for cell fusion and thus constitute the “core fusion machinery” of HCMV, which is conserved among other herpesviruses. Thus, the four glycoprotein complexes play a crucial role in viral attachment, binding, fusion and entry into the host cell. The disclosure provides HCMV mRNA vaccines containing mRNAs encoding the hCMV pentamer (gH, gL, UL128, UL130, and UL131A) and gB in lipid nanoparticle. The hCMV immunogenic compositions may comprise (a) a messenger ribonucleic acid (mRNA) polynucleotide comprising an open reading frame encoding a hCMV gH polypeptide; (b) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gL polypeptide; (c) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL128 polypeptide; (d) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL130 polypeptide; (e) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL131A polypeptide; and (f) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gB polypeptide Each of the individual mRNAs encoding the hCMV pentamer (gH, gL, UL128, UL130, and UL131A) and gB may be included in the composition at equal mass ratios (e.g., an mRNA mass ratio for gH:gL:UL128:UL130:UL131A:gB of approximately 1:1:1:1:1:1). In some embodiments an approximately equal molar ratio of gL, UL128, UL130, and UL131A, and increased molar ratios of gB and/or gH relative to the other mRNA components within an hCMV immunogenic composition is provided. In some embodiments the molar ratio of (a):(f) within the immunogenic composition is about 1:1; the molar ratio of (b):(c):(d):(e) within the immunogenic composition is about 1:1:1:1; and the molar ratio of each of (a) and (f) to any one of (b), (c), (d) or (e) within the immunogenic composition is about 1.5:1 to 2:1. In some embodiments, the molar ratio of (a):(b):(c):(d):(e):(f) is about 2:1:1:1:1:2. In some embodiments, the molar ratio of each of (a) and (f) to any one of (b), (c), (d) or (e) within the immunogenic composition is about 1.5:1 to 2:1 (e.g., 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, or 2:1). In some embodiments, the molar ratio of (a) to any one of (b), (c), (d) or (e) within the immunogenic composition is about 1.5:1 to 2:1 (e.g., 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, or 2:1). In some embodiments, the molar ratio of (f) to any one of (b), (c), (d) or (e) within the immunogenic composition is about 1.5:1 to 2:1 (e.g., 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, or 2:1). In some embodiments, the molar ratio of (a) to any one of (b), (c), (d) or (e) within the immunogenic composition is about 1.5:1 to 2:1 (e.g., 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, or 2:1), and the molar ratio of (f) to any one of (b), (c), (d) or (e) within the immunogenic composition is about 1.5:1 to 2:1 (e.g., 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, or 2:1). In some embodiments, the molar ratio of (a):(b):(c):(d):(e):(f) is about 1.5:1:1:1:1:1.5. In some embodiments, the molar ratio of (a):(b):(c):(d):(e):(f) is about 2:1:1:1:1:2 In some embodiments, the hCMV vaccine components comprise the sequences provided in Table 1. In some embodiments, the mRNA encoding hCMV gH protein comprises a nucleotide sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the nucleotide sequence of sequence of SEQ ID NO: 5. In some embodiments, the mRNA encoding hCMV gL protein comprises a nucleotide sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the nucleotide sequence of sequence of SEQ ID NO: 6. In some embodiments, the mRNA encoding hCMV UL128 protein comprises a nucleotide sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the nucleotide sequence of sequence of SEQ ID NO: 2. In some embodiments, the mRNA encoding hCMV UL130 protein comprises a nucleotide sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the nucleotide sequence of sequence of SEQ ID NO: 3. In some embodiments, the mRNA encoding hCMV UL131A protein comprises a nucleotide sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the nucleotide sequence of sequence of SEQ ID NO: 4. In some embodiments, the mRNA encoding hCMV gB protein comprises a nucleotide sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the nucleotide sequence of sequence of SEQ ID NO: 1. In some embodiments, the mRNA encoding the hCMV gH polypeptide comprises the nucleotide sequence of SEQ ID NO: 5. In some embodiments, the mRNA encoding the hCMV gL polypeptide comprises the nucleotide sequence of SEQ ID NO: 6. In some embodiments, the mRNA encoding the hCMV UL128 polypeptide comprises the nucleotide sequence of SEQ ID NO: 2. In some embodiments, the mRNA encoding the hCMV UL130 polypeptide comprises the nucleotide sequence of SEQ ID NO: 3. In some embodiments, the mRNA encoding the hCMV UL131A polypeptide comprises the nucleotide sequence of SEQ ID NO: 4. In some embodiments, the mRNA encoding the hCMV gB polypeptide comprises the nucleotide sequence of SEQ ID NO: 1. In some embodiments, the open reading frame encoding the hCMV gH polypeptide comprises a sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the sequence of SEQ ID NO: 11. In some embodiments, the open reading frame encoding the hCMV gL polypeptide comprises a sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the sequence of SEQ ID NO: 12. In some embodiments, the open reading frame encoding the hCMV UL128 polypeptide comprises a sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the sequence of SEQ ID NO: 8. In some embodiments, the open reading frame encoding the hCMV UL130 polypeptide comprises a sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the sequence of SEQ ID NO: 9. In some embodiments, the open reading frame encoding the hCMV UL131A polypeptide comprises a sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the sequence of SEQ ID NO: 10. In some embodiments, the open reading frame encoding the gB polypeptide comprises a sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the sequence of SEQ ID NO: 7. In some embodiments, the mRNA encoding the hCMV gH polypeptide comprises an open reading frame (ORF) of the nucleotide sequence of SEQ ID NO: 11. In some embodiments, the mRNA encoding the hCMV gL polypeptide comprises an open reading frame (ORF) of the nucleotide sequence of SEQ ID NO: 12. In some embodiments, the mRNA encoding the hCMV UL128 polypeptide comprises an open reading frame (ORF) of the nucleotide sequence of SEQ ID NO: 8. In some embodiments, the mRNA encoding the hCMV UL130 polypeptide comprises an open reading frame (ORF) of the nucleotide sequence of SEQ ID NO: 9. In some embodiments, the mRNA encoding the hCMV UL131A polypeptide comprises an open reading frame (ORF) of the nucleotide sequence of SEQ ID NO: 10. In some embodiments, the mRNA encoding the hCMV gB polypeptide comprises an open reading frame (ORF) of the nucleotide sequence of SEQ ID NO: 7. In some embodiments, the hCMV gH polypeptide comprises an amino acid sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the hCMV gL polypeptide comprises an amino acid sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the hCMV UL128 polypeptide comprises an amino acid sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the hCMV UL130 polypeptide comprises an amino acid sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the amino acid sequence of SEQ ID NO: 17. In some embodiments, the hCMV UL131A polypeptide comprises an amino acid sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the hCMV gB polypeptide comprises an amino acid sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity, or more than 99% identity, to the amino acid sequence of SEQ ID NO: 15. In some embodiments, the hCMV gH polypeptide comprises the amino acid sequence of SEQ ID NO: 19. In some embodiments, the hCMV gL polypeptide comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments, the hCMV UL128 polypeptide comprises the amino acid sequence of SEQ ID NO: 16. In some embodiments, the hCMV UL130 polypeptide comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the hCMV UL131A polypeptide comprises the amino acid sequence of SEQ ID NO: 18. In some embodiments, the hCMV gB polypeptide comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, the mRNA components of a hCMV immunogenic composition (e.g., mRNA vaccine) are present in equal masses. In other embodiments, the mRNA components of a hCMV immunogenic composition (e.g., mRNA vaccine) are not present in equal masses. It should be understood that the hCMV immunogenic compositions (e.g., mRNA vaccines) of the present disclosure may comprise a signal sequence. It should also be understood that the hCMV mRNA vaccines of the present disclosure may include any 5’ untranslated region (UTR) and/or any 3’ UTR. Exemplary UTR sequences are provided in Table 1; however, other UTR sequences may be used or exchanged for any of the UTR sequences described herein. UTRs may also be omitted from the vaccine constructs provided herein. In some embodiments, “administering” or “administration” means providing a material to a subject in a manner that is pharmacologically useful. In some embodiments, a composition disclosed herein is administered to a subject enterally. In some embodiments, an enteral administration of the composition is oral. In some embodiments, a composition disclosed herein is administered to the subject parenterally. In some embodiments, a composition disclosed herein is administered to a subject subcutaneously, intraocularly, intravitreally, subretinally, intravenously (IV), intracerebro-ventricularly, intramuscularly, intrathecally (IT), intracisternally, intraperitoneally, via inhalation, topically, or by direct injection to one or more cells, tissues, or organs. To "treat" a disease as the term is used herein, means to reduce the frequency or severity of at least one sign or symptom of a disease, disorder or condition experienced by a subject. The compositions described above or elsewhere herein are typically administered to a subject in an effective amount, that is, an amount capable of producing a desirable result. The desirable result will depend upon the active agent being administered. For example, an effective amount of a composition comprising a nucleic acid (e.g., mRNA) formulated in a lipid (e.g., LNP) may be an amount of the composition that is capable of increasing expression of a protein in the subject. A therapeutically acceptable amount may be an amount that is capable of treating a disease or condition, e.g., a disease or condition that that can be relieved by increasing expression of a protein in a subject. As is well known in the medical and veterinary arts, dosage for any one subject depends on many factors, including the subject's size, body surface area, age, the particular composition to be administered, the active ingredient(s) in the composition, the intended outcome of the administration, time and route of administration, general health, and other drugs being administered concurrently. In some embodiments, a subject is administered a composition comprising a nucleic acid (e.g., mRNA) formulated in a lipid (e.g., LNP) in an amount sufficient to increase expression of a protein in the subject. In certain embodiments, LNP preparations (e.g., populations or formulations) are analyzed for polydispersity in size (e.g., particle diameter) and/or composition (e.g., amino lipid amount or concentration, phospholipid amount or concentration, structural lipid amount or concentration, PEG-lipid amount or concentration, mRNA amount (e.g., mass) or concentration) and, optionally, further assayed for in vitro and/or in vivo activity. Fractions or pools thereof can also be analyzed for accessible mRNA and/or purity (e.g., purity as determined by reverse-phase (RP) chromatography). Particle size (e.g., particle diameter) can be determined by Dynamic Light Scattering (DLS). DLS measures a hydrodynamic diameter. Smaller particles diffuse more quickly, leading to faster fluctuations in the scattering intensity and shorter decay times for the autocorrelation function. Larger particles diffuse more slowly, leading to slower fluctuations in the scattering intensity and longer decay times in the autocorrelation function. mRNA purity can be determined by high-performance liquid chromatography (HPLC) (e.g., reverse phase high-performance liquid chromatography (RP-HPLC) or reverse phase high- performance liquid chromatography (RP-HPLC) size based separation) or capillary electrophoresis (CE) (e.g., frontal analysis capillary electrophoresis (FA-CE)). Reverse phase high-performance liquid chromatography (RP-HPLC) size based separation can be used to assess mRNA integrity by a length-based gradient RP separation and UV detection of RNA at 260 nm. As used herein “main peak” or “main peak purity” refers to the RP-HPLC signal detected from mRNA that corresponds to the full size mRNA molecule loaded within a given LNP formulation. mRNA purity can also be assessed by fragmentation analysis. Fragmentation analysis (FA) is a method by which nucleic acid (e.g., mRNA) fragments can be analyzed by capillary electrophoresis. Fragmentation analysis involves sizing and quantifying nucleic acids (e.g., mRNA), for example by using an intercalating dye coupled with an LED light source. Such analysis may be completed, for example, with a Fragment Analyzer from Advanced Analytical Technologies, Inc. Compositions formed via the methods described herein may be particularly useful for administering an agent to a subject in need thereof. In some embodiments, the compositions are used to deliver a pharmaceutically active agent. In some instances, the compositions are used to deliver a prophylactic agent. The compositions may be administered in any way known in the art of drug delivery, for example, orally, parenterally, intravenously, intramuscularly, subcutaneously, intradermally, transdermally, intrathecally, submucosally, sublingually, rectally, vaginally, etc. Once the compositions have been prepared, they may be combined with pharmaceutically acceptable excipients to form a pharmaceutical composition. As would be appreciated by one of skill in this art, the excipients may be chosen based on the route of administration as described below, the agent being delivered, and the time course of delivery of the agent. Pharmaceutical compositions described herein and for use in accordance with the embodiments described herein may include a pharmaceutically acceptable excipient. As used herein, the term “pharmaceutically acceptable excipient” means a non-toxic, inert solid, semi- solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Some examples of materials which can serve as pharmaceutically acceptable excipients are sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, methylcellulose, hydroxypropylmethylcellulose, ethyl cellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols such as propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; detergents such as Tween 80; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen free water; isotonic saline; citric acid, acetate salts, Ringer’s solution; ethyl alcohol; and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. The pharmaceutical compositions of this invention can be administered to humans and/or to animals, orally, rectally, parenterally, intracisternally, intravaginally, intranasally, intraperitoneally, topically (as by powders, creams, ointments, or drops), bucally, or as an oral or nasal spray. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active ingredients (i.e., the particles), the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension, or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer’s solution, ethanol, U.S.P., and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. The injectable formulations can be sterilized, for example, by filtration through a bacteria retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. Compositions for rectal or vaginal administration may be suppositories which can be prepared by mixing the particles with suitable non irritating excipients or carriers such as cocoa butter, polyethylene glycol, or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the particles. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the particles are mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets, and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragées, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Dosage forms for topical or transdermal administration of a pharmaceutical composition include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, or patches. The particles are admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, and eye drops are also possible. The ointments, pastes, creams, and gels may contain, in addition to the compositions of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc, and zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to the compositions of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates, and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants such as chlorofluorohydrocarbons. Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compositions in a proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compositions in a polymer matrix or gel. In other embodiments, the stabilized compositions of the invention are loaded and stored in prefilled syringes and cartridges for patient-friendly autoinjector and infusion pump devices. Kits for use in preparing or administering the compositions are also provided. A kit for forming compositions may include any solvents, solutions, buffer agents, acids, bases, salts, targeting agent, etc. needed in the composition formation process. Different kits may be available for different targeting agents. In certain embodiments, the kit includes materials or reagents for purifying, sizing, and/or characterizing the resulting compositions. The kit may also include instructions on how to use the materials in the kit. The one or more agents (e.g., pharmaceutically active agent) to be contained within the composition are typically provided by the user of the kit. Kits are also provided for using or administering the compositions. The compositions may be provided in convenient dosage units for administration to a subject. The kit may include multiple dosage units. For example, the kit may include 1-100 dosage units. In certain embodiments, the kit includes a week supply of dosage units, or a month supply of dosage units. In certain embodiments, the kit includes an even longer supply of dosage units. The kits may also include devices for administering the compositions. Exemplary devices include syringes, spoons, measuring devices, etc. The kit may optionally include instructions for administering the compositions (e.g., prescribing information). The term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy- ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium, and N + (C 1-4 alkyl) 4 − salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. As disclosed herein, the terms “composition” and “formulation” are used interchangeably. In some embodiments, article A comprises a liquid pharmaceutical composition comprising RNA formulated in a lipid nanoparticle, liposome, or lipoplex; wherein the article has a shelf-life of at least three months when stored at a temperature of greater than 0 °C and less than or equal to 10 °C; wherein the amount is greater than or equal to (1 + the fraction of the RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the liquid pharmaceutical composition); and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. According to some embodiments of article A, the article comprises a total amount of full length RNA, and the total amount of full length RNA is greater than or equal to (1 + the fraction of the full length RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the full length RNA) x (the number of individual doses of the liquid pharmaceutical composition in the article). In certain embodiments, article AA comprises a liquid pharmaceutical composition comprising RNA formulated in a lipid nanoparticle, liposome, or lipoplex; wherein the article has a shelf-life of at least three months when stored at a temperature of greater than 0 °C and less than or equal to 10 °C; wherein the article comprises a total amount of full length RNA, and the total amount of full length RNA is greater than or equal to (1 + the fraction of the full length RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the full length RNA) x (the number of individual doses of the liquid pharmaceutical composition in the article; and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. In certain embodiments of articles A and/or AA, the article further comprises a label, suggesting an amount of the liquid pharmaceutical composition to be administered to a subject. In some embodiments of articles A and/or AA, the article comprises a vial, a syringe, a cartridge, an infusion pump, and/or a light protective container. In certain embodiments of articles A and/or AA, the amount is greater than or equal to 1.05 x (an individual dose of the liquid pharmaceutical composition) and/or greater than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition). In some embodiments of articles A and/or AA, the amount is less than or equal to 2.00 x (an individual dose of the liquid pharmaceutical composition). In accordance with certain embodiments of articles A and/or AA, the RNA is encapsulated within the lipid nanoparticle, liposome, or lipoplex. According to some embodiments of articles A and/or AA, the lipid nanoparticle, liposome, or lipoplex comprises a lipid nanoparticle. In certain embodiments of articles A and/or AA, the lipid nanoparticle, liposome, or lipoplex comprises a liposome. In some embodiments of articles A and/or AA, the lipid nanoparticle, liposome, or lipoplex comprises a lipoplex. According to certain embodiments, article B comprises a liquid pharmaceutical composition comprising an RNA encoding one or more hCMV antigens formulated in a lipid carrier housed in a container; wherein the container comprises a total amount of RNA and wherein the total amount of RNA includes 40%-95% intact RNA and 5%-60% RNA that is less than full length RNA. In some embodiments the composition comprises 40%-95% pure RNA. In some embodiments of article B, the percentage of intact RNA is greater than or equal to 15% + the percentage of the RNA that would degrade in the liquid pharmaceutical composition over a shelf-life of the article. In certain embodiments of article B, the article comprises at least 5% more intact RNA than a minimum therapeutically effective dose of the intact RNA. In some embodiments of article B, the total amount of RNA includes 40%-80% intact RNA and 20%-60% RNA that is less than full length RNA. In certain embodiments of article B, the total amount of RNA includes 40%-70% intact RNA and 30%-60% RNA that is less than full length RNA. In accordance with some embodiments of article B, the total amount of RNA includes 60%-80% intact RNA and 20%-40% RNA that is less than full length RNA. According to certain embodiments of article B, the total amount of RNA includes 70%-95% intact RNA and 5%-30% RNA that is less than full length RNA. In some embodiments of article B, the total amount of RNA includes 75-90% intact RNA and 10%-25% RNA that is less than full length RNA. In certain embodiments of article B, the total amount of RNA includes 75-80% intact RNA and 20%-25% RNA that is less than full length RNA. In some embodiments of article B, the article further comprises a label on the container, wherein the label identifies a number of individual doses of the liquid pharmaceutical composition housed in the container, an amount of each individual dose of the liquid pharmaceutical composition to be administered to a subject, and an effective dose of RNA within the liquid pharmaceutical composition within each individual dose, wherein the container comprises a total amount of RNA, wherein the total amount of RNA has a value of at least the number of individual doses in the container times 5% greater than the amount of the effective dose of RNA within each individual dose. In certain embodiments, article C comprises a liquid pharmaceutical composition comprising an RNA formulated in a lipid carrier housed in a container; wherein the container comprises a total amount of RNA, wherein the total amount of RNA has a value of at least a number of individual doses in the container times 5% greater than the amount of the effective dose of RNA within each individual dose; and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. According to some embodiments of article C, the container comprises a total amount of full length RNA, wherein the total amount of full length RNA is at least the number of individual doses in the container times 5% greater than the amount of the effective dose of full length RNA within each individual dose. In some embodiments of article C, the article further comprises a label on the container, wherein the label identifies the number of individual doses of the liquid pharmaceutical composition housed in the container, an amount of each individual dose of the liquid pharmaceutical composition to be administered to a subject, and an effective dose of RNA within the liquid pharmaceutical composition within each individual dose. According to certain embodiments of articles B and/or C, the total amount of RNA has a value of at least the number of individual doses in the container times 20% greater than the amount of the effective dose of RNA within each individual dose. In accordance with some embodiments of articles B and/or C, the total amount of RNA has a value of at least the number of individual doses in the container times 30% greater than the amount of the effective dose of RNA within each individual dose. In some embodiments of articles B and/or C, the total amount of RNA has a value of less than or equal to the number of individual doses in the container times 100% greater than the amount of the effective dose of RNA within each individual dose. In accordance with certain embodiments of articles B and/or C, the article has a shelf-life of at least one month when stored at a temperature of greater than 0 °C and less than or equal to 10 °C. According to some embodiments of articles B and/or C, the article has a shelf-life of at least three months when stored at a temperature of greater than 0 °C and less than or equal to 10 °C. In some embodiments of articles A, AA, B and/or C, the article has a shelf-life of at least one month when stored at a temperature of 5 °C. In certain embodiments of articles A, AA, B, and/or C, the article has a shelf-life of at least three months when stored at a temperature of 5 °C. According to some embodiments of articles A, AA, B and/or C, at least 40% of the total amount of RNA in the liquid pharmaceutical composition is intact if stored for three months at 5 °C. In accordance with certain embodiments of articles A, AA, B and/or C at least 50% of the total amount of RNA in the liquid pharmaceutical composition is intact if stored for three months at 5 °C. In some embodiments of articles A, AA, B and/or C, at least 60% of the total amount of RNA in the liquid pharmaceutical composition is intact if stored for three months at 5 °C. In certain embodiments of articles A, AA, B and/or C, at least 70% of the total amount of RNA in the liquid pharmaceutical composition is intact if stored for three months at 5 °C. In accordance with some embodiments of articles A, AA, B and/or C, at least 90% of the total amount of RNA in the liquid pharmaceutical composition is intact if stored for three months at 5°C. In certain embodiments of articles B and/or C, the container comprises a light protective container. In some embodiments of articles B and/or C, the container comprises a vial, a syringe, a cartridge, and/or an infusion pump. According to some embodiments or articles B and/or C, the RNA is encapsulated within the lipid carrier. In some embodiments of articles A, AA, B and/or C, the label indicates that the article should not be stored at the glass transition temperature of the liquid pharmaceutical composition. In certain embodiments of articles A, AA, B and/or C, the label indicates that the article should not be stored at a temperature of less than or equal to -20 °C and greater than or equal to -50 °C. According to some embodiments of articles A, AA, B and/or C, the label indicates that the article should not be stored at a temperature of less than or equal to -30 °C and greater than or equal to - 35 °C. In accordance with certain embodiments of articles A, AA, B and/or C, the lipid carrier comprises a lipid nanoparticle. According to certain embodiments of B and/or C, the lipid carrier comprises a liposome. In some embodiments of B and/or C, the lipid carrier comprises a lipoplex. In certain embodiments of articles A, AA, B and/or C, the individual dose of the liquid pharmaceutical composition is the individual dose needed to produce a therapeutically effective amount of a protein in the subject. In accordance with some embodiments of articles A, AA, B and/or C, the individual dose of the liquid pharmaceutical composition is the individual dose approved by the FDA to stimulate an antigen specific immune response in the subject. According to some embodiments of articles A, AA, B and/or C, the lipid nanoparticle comprises a ratio of 20-60% amino lipids, 5-30% phospholipid, 10-55% structural lipid, and 0.5- 15% PEG-modified lipid. In accordance with certain embodiments of articles A, AA, B and/or C, the lipid nanoparticle comprises a ratio of 20-60% amino lipids, 5-25% phospholipid, 25-55% structural lipid, and 0.5-15% PEG-modified lipid. In some embodiments of articles A, AA, B and/or C, the RNA comprises mRNA. In certain embodiments of articles A, AA, B and/or C, the RNA comprises greater than or equal to 400, 500, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, or 10,000 nucleotides. For example, in some embodiments of articles A, AA, B and/or C, the RNA comprises greater than or equal to 400 nucleotides. According to certain embodiments of articles A, AA, B and/or C, the RNA comprises greater than or equal to 4,000 nucleotides. In accordance with some embodiments of articles A, AA, B and/or C, the RNA comprises less than or equal to 20,000, 15,000, 14,000, 13,000, 12,000, 11,000, 10,000, 9000, 8000, 7000, or 6000 nucleotides. For example, in certain embodiments of articles A, AA, B and/or C, the RNA comprises less than or equal to 10,000 nucleotides. In some embodiments of articles A, AA, B and/or C, the RNA comprises less than or equal to 6,000 nucleotides. In certain embodiments of articles A, AA, B and/or C, the liquid pharmaceutical composition is formulated in an aqueous solution. According to certain embodiments of articles A, AA, B and/or C, the mRNA encodes one or more hCMV antigens. In some embodiments of articles A, AA, B and/or C, the one or more hCMV antigens comprises greater than or equal to 1 and less than or equal to 6 hCMV antigens. In some embodiments of articles A, AA, B and/or C, the article comprises a total amount of the liquid pharmaceutical composition, wherein the total amount is 1.25 x 10 individual doses x (an individual dose of the liquid pharmaceutical composition), and wherein the RNA is an mRNA that encodes a human cytomegalovirus (hCMV) antigen. In certain embodiments of articles A, AA, B and/or C, the RNA comprises a nucleotide sequence having at least 80% identity, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. In accordance with some embodiments of articles A, AA, B and/or C, the RNA comprises a nucleotide sequence having at least 90% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. In accordance with certain embodiments of articles A, AA, B, and/or C, the RNA encoding the one or more hCMV antigens comprises (a) a messenger ribonucleic acid (mRNA) polynucleotide comprising an open reading frame encoding a hCMV gH polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 5 and/or 11); (b) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gL polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 6 and/or 12); (c) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL128 polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 2 and/or 8); (d) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL130 polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 3 and/or 9); (e) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL131A polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 4 and/or 10); and/or (f) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gB polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 1 and/or 7). In some embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (a):(b):(c):(d):(e):(f) is about 1: . In certain embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (b):(c):(d):(e) is about 1:1:1:1. In some embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (a):(f) is about 1:1. In certain embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of each of (a) and (f) to one or more (e.g., all) of (b), (c), (d), and/or (e) is about 1.5:1 to 2:1. In some embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (a):(b):(c):(d):(e):(f) is about 2:1:1:1:1:2. In certain embodiments, pharmaceutical composition A comprises mRNA encapsulated in a lipid nanoparticle, wherein the composition comprises a total amount of intact mRNA that is greater than an effective amount of intact mRNA, and wherein the composition comprises at least the effective amount of the intact mRNA after storage of the composition for a period of time; and wherein the mRNA encodes one or more human cytomegalovirus (hCMV) antigens. In accordance with some embodiments of pharmaceutical composition A, the total amount of intact mRNA decreases in the composition after storage of the composition for the period of time. According to certain embodiments of pharmaceutical composition A, the total amount of intact mRNA is calculated to account for degradation of the mRNA during the storage of the composition for the period of time. According to some embodiments of pharmaceutical composition A, the degradation is from transesterification of the intact mRNA. In accordance with certain embodiments of pharmaceutical composition A, the degradation is greater than or equal to 5%, greater than or equal to 7%, greater than or equal to 8%, greater than or equal to 9%, greater than or equal to 10%, or greater than or equal to 12% of the total mRNA in the composition per month. In certain embodiments of pharmaceutical composition A, the period of time is greater than or equal to 1 month, greater than or equal to 2 months, greater than or equal to 3 months, greater than or equal to 6 months, or greater than or equal to 9 months. In some embodiments of pharmaceutical composition A, the storage is at a temperature of from about 0°C to about 10°C, such as at about 5°C. In accordance with some embodiments of pharmaceutical composition A, the total amount of intact mRNA is at least 40%, such as at least 50%, at least 55%, at least 60%, at least 63%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% of the total mRNA in the composition. In certain embodiments of pharmaceutical composition A, the effective amount of intact mRNA is at least about 15%, such as at least about 18%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, or at least about 55% of the total mRNA in the composition. In some embodiments of pharmaceutical composition A, the pharmaceutical composition comprises at least 50% intact mRNA of the total mRNA in the composition following storage of the composition for 3 months at about 5°C. In certain embodiments of pharmaceutical composition A, the effective amount comprises at least 5 micrograms of the intact mRNA, such as at least 10 micrograms, at least 20 micrograms, at least 30 micrograms, at least 40 micrograms, at least 50 micrograms, at least 60 micrograms, at least 70 micrograms, at least 80 micrograms, at least 90 micrograms, at least 100 micrograms, at least 125 micrograms, or at least 150 micrograms of the intact mRNA. According to certain embodiments of pharmaceutical composition A, the one or more hCMV antigens comprises greater than or equal to 1 and less than or equal to 6 hCMV antigens. In accordance with some embodiments of pharmaceutical composition A, the mRNA comprises a nucleotide sequence having at least 80% identity, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. In certain embodiments of pharmaceutical composition A, the mRNA comprises a nucleotide sequence having at least 90% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. In accordance with certain embodiments of pharmaceutical composition A, the RNA encoding the one or more hCMV antigens comprises (a) a messenger ribonucleic acid (mRNA) polynucleotide comprising an open reading frame encoding a hCMV gH polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 5 and/or 11); (b) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gL polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 6 and/or 12); (c) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL128 polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 2 and/or 8); (d) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL130 polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 3 and/or 9); (e) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL131A polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 4 and/or 10); and/or (f) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gB polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 1 and/or 7). In some embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (a):(b):(c):(d):(e):(f) is about 1:1:1:1:1:1. In certain embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (b):(c):(d):(e) is about 1:1:1:1. In some embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (a):(f) is about 1:1. In certain embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of each of (a) and (f) to one or more (e.g., all) of (b), (c), (d), and/or (e) is about 1.5:1 to 2:1. In some embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (a):(b):(c):(d):(e):(f) is about 2:1:1:1:1:2. In some embodiments, a container (such as a vial, a syringe, a cartridge, an infusion pump, and/or a light protective container) comprises pharmaceutical composition A. In certain embodiments of articles A, AA, B, and/or C, the pharmaceutical composition comprises pharmaceutical composition A. In some embodiments, method A of filling an article comprises adding RNA formulated in a lipid nanoparticle, liposome, or lipoplex to the article to form an amount of a liquid pharmaceutical composition in the article; wherein the amount of RNA is greater than or equal to (1 + the fraction of the RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the liquid pharmaceutical composition) x (the number of individual doses in the article); and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. In accordance with some embodiments of method A, wherein the adding RNA formulated in a lipid nanoparticle, liposome, or lipoplex to the article forms an amount of full length RNA in the article, and wherein the amount of full length RNA is greater than or equal to (1 + the fraction of the RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the full length RNA) x (the number of individual doses in the article). According to certain embodiments of method A, the RNA and/or lipid nanoparticle, liposome, or lipoplex are frozen prior to addition to the article. In accordance with certain embodiments of method A, the article is stored at a temperature of greater than 0 °C and less than 10 °C for up to 1 year. According to some embodiments of method A, the article is stored at a temperature of greater than 0 °C and less than 10 °C for up to 3 months. In some embodiments of method A, at least 40% of the amount of the RNA in the liquid pharmaceutical composition is intact if stored for three months at a temperature of greater than 0 °C and less than 10 °C. In certain embodiments of method A, at least 50% of the amount of the RNA in the liquid pharmaceutical composition is intact if stored for three months at a temperature of greater than 0 °C and less than 10 °C. According to some embodiments of method A, the liquid pharmaceutical composition comprises pharmaceutical composition A. In accordance with some embodiments of method A, at least 60% of the amount of the RNA in the liquid pharmaceutical composition is intact if stored for three months at a temperature of greater than 0 °C and less than 10 °C. In certain embodiments of method A, at least 70% of the amount of RNA in the liquid pharmaceutical composition is intact if stored for three months at a temperature of greater than 0 °C and less than 10 °C. According to certain embodiments of method A, at least 75% of the amount of RNA in the liquid pharmaceutical composition is intact if stored for three months at a temperature of greater than 0 °C and less than 10 °C. In some embodiments of method A, the temperature is 5 °C. In certain embodiments of method A, the article is not stored at the glass transition temperature of the liquid pharmaceutical composition. In some embodiments of method A, the article is not stored at less than or equal to -20 °C and greater than or equal to -50 °C. In accordance with certain embodiments of method A, the article is not stored at less than or equal to -30 °C and greater than or equal to -35 °C. According to certain embodiments of method A, the amount of RNA is greater than or equal to 1.05 x (an individual dose of the liquid pharmaceutical composition) x (the number of individual doses in the article). In accordance with some embodiments of method A, the amount of RNA is greater than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition) x (the number of individual doses in the article). In certain embodiments of method A, the amount of RNA is less than or equal to 2.00 x (an individual dose of the liquid pharmaceutical composition) x (the number of individual doses in the article). In some embodiments of method A, the article comprises a vial, a syringe, a cartridge, an infusion pump, and/or a light protective container. In accordance with certain embodiments of method A, the amount is 1.25 x 10 individual doses x (an individual dose of the liquid pharmaceutical composition), and wherein the RNA is an mRNA that encodes one or more human cytomegalovirus (hCMV) antigens. According to some embodiments, method B of delivering an effective dose of an RNA to a subject, comprises administering a liquid pharmaceutical composition comprising an RNA formulated in a lipid carrier to a subject, wherein a total dose of the RNA is administered to the subject, and wherein the total dose of RNA administered to the subject is at least 5% greater than the effective dose of the RNA; and wherein the RNA encodes one or more human cytomegalovirus (hCMV) antigens. In certain embodiments of method B, the liquid pharmaceutical composition comprises pharmaceutical composition A. In certain embodiments of method B, the total dose of RNA administered to the subject is at least 20% greater than the effective dose of the RNA. In accordance with some embodiments of method B, the total dose of RNA administered to the subject is at least 30% greater than the effective dose of the RNA. In some embodiments of method B, the total dose of the RNA administered to the subjected is less than or equal to 100% greater than the effective dose of the RNA. According to certain embodiments of method B, the lipid carrier comprises a lipid nanoparticle, liposome, or lipoplex. In certain embodiments of methods A and/or B, the RNA is encapsulated within the lipid nanoparticle, liposome, or lipoplex in the liquid pharmaceutical composition. In some embodiments of methods A and/or B, the lipid nanoparticle, liposome, or lipoplex comprises a lipid nanoparticle. In certain embodiments of methods A and/or B, the lipid nanoparticle, liposome, or lipoplex comprises a liposome. According to some embodiments of methods A and/or B, the lipid nanoparticle, liposome, or lipoplex comprises a lipoplex. In accordance with certain embodiments of methods A and/or B, the individual dose of the liquid pharmaceutical composition is the individual dose needed to produce a therapeutically effective amount of a protein in the subject. According to some embodiments of methods A and/or B, the individual dose of the liquid pharmaceutical composition is the individual dose approved by the FDA to stimulate an antigen specific immune response in the subject. In accordance with some embodiments of methods A and/or B, the lipid nanoparticle comprises a ratio of 20-60% amino lipids, 5-30% phospholipid, 10-55% structural lipid, and 0.5- 15% PEG-modified lipid. In certain embodiments of methods A and/or B, the lipid nanoparticle comprises a ratio of 20-60% amino lipids, 5-25% phospholipid, 25-55% structural lipid, and 0.5- 15% PEG-modified lipid. In some embodiments of methods A and/or B, the RNA comprises mRNA. In certain embodiments of methods A and/or B, the RNA comprises greater than or equal to 400, 500, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, or 10,000 nucleotides. For example, in some embodiments of methods A and/or B, the RNA comprises greater than or equal to 400 nucleotides. In accordance with certain embodiments of methods A and/or B, the RNA comprises greater than or equal to 4,000 nucleotides. According to some embodiments of methods A and/or B, the RNA comprises less than or equal to 20,000, 15,000, 14,000, 13,000, 12,000, 11,000, 10,000, 9000, 8000, 7000, or 6000 nucleotides. For example, in certain embodiments of methods A and/or B, the RNA comprises less than or equal to 10,000 nucleotides. In accordance with some embodiments of methods A and/or B, the RNA comprises less than or equal to 6,000 nucleotides. In certain embodiments of methods A and/or B, the liquid pharmaceutical composition is formulated in an aqueous solution. In accordance with some embodiments of methods A and/or B, the mRNA encodes one or more hCMV antigens. In some embodiments of methods A and/or B, the one or more hCMV antigens comprises greater than or equal to 1 and less than or equal to 6 hCMV antigens. In accordance with certain embodiments of methods A and/or B, the RNA comprises a nucleotide sequence having at least 80% identity, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. According to some embodiments of methods A and/or B, the RNA comprises a nucleotide sequence having at least 90% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. In some embodiments, method C of compensating for transesterification of mRNA in a composition comprising the mRNA encapsulated by a lipid nanoparticle comprises preparing the composition with increased mRNA purity as compared to an mRNA purity that will be present in the composition after storage of the composition, such that the amount of mRNA present in the composition after storage will comprise an effective amount of the mRNA, and wherein the mRNA encodes one or more hCMV antigens. According to some embodiments of method C, the composition comprises pharmaceutical composition A. In certain embodiments of method C, the one or more hCMV antigens comprises greater than or equal to 1 and less than or equal to 6 hCMV antigens. In accordance with certain embodiments of method C, the mRNA comprises a nucleotide sequence having at least 80% identity, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. According to some embodiments of method C, the mRNA comprises a nucleotide sequence having at least 90% identity to SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12. In accordance with certain embodiments of methods A, B, and/or C, the RNA encoding the one or more hCMV antigens comprises (a) a messenger ribonucleic acid (mRNA) polynucleotide comprising an open reading frame encoding a hCMV gH polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 5 and/or 11); (b) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gL polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 6 and/or 12); (c) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL128 polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 2 and/or 8); (d) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL130 polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 3 and/or 9); (e) a mRNA polynucleotide comprising an open reading frame encoding a hCMV UL131A polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 4 and/or 10); and/or (f) a mRNA polynucleotide comprising an open reading frame encoding a hCMV gB polypeptide (e.g., an mRNA comprising SEQ ID. NOs: 1 and/or 7). In some embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (a):(b):(c):(d):(e):(f) is about 1:1:1:1:1:1. In certain embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (b):(c):(d):(e) is about 1:1:1:1. In some embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (a):(f) is about 1:1. In certain embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of each of (a) and (f) to one or more (e.g., all) of (b), (c), (d), and/or (e) is about 1.5:1 to 2:1. In some embodiments where the RNA encoding the one or more hCMV antigens comprises (a), (b), (c), (d), (e), and/or (f), the molar ratio of (a):(b):(c):(d):(e):(f) is about 2:1:1:1:1:2. SEQUENCE LISTING It should be understood that any of the mRNA sequences described herein may include a 5′ UTR and/or a 3′ UTR. The UTR sequences may be selected from the following sequences, or other known UTR sequences may be used. It should also be understood that any of the mRNA constructs described herein may further comprise a polyA tail and/or cap (e.g., 7mG(5’)ppp(5’)NlmpNp). Further, while many of the mRNAs and encoded antigen sequences described herein include a signal peptide and/or a peptide tag (e.g., C-terminal His tag), it should be understood that the indicated signal peptide and/or peptide tag may be substituted for a different signal peptide and/or peptide tag, or the signal peptide and/or peptide tag may be omitted. Table 1
The following examples are intended to illustrate certain embodiments of the present invention, but do not exemplify the full scope of the invention. Without further elaboration, it is believed that one skilled in the art can, based on the above description, utilize the present invention to its fullest extent. The following specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. EXAMPLES EXAMPLE 1 This example describes the degradation of mRNA in lipid nanoparticle formulations when stored for 3 months at 5 °C. This example demonstrates that the main mechanism of degradation of mRNA in lipid nanoparticle formulations at these conditions is trans-esterification (rather than hydrolysis). In transesterification, 2ʹ-hydroxyl moieties of ribose rings along the mRNA’s backbone nucleophilically attack their adjacent phosphates to form cyclic pentavalent phosphorus intermediates. These transient intermediates then collapse, either leading to 2ʹ-5ʹ-phosphodiester linkages (backbone isomerization, which is not discussed here), or leading to strand scission, resulting in fragment strands that are terminated by 2ʹ-3ʹ-cyclic phosphates on their 3ʹ-ends (see FIG.1A). On the other hand, in hydrolysis, water nucleophilically attacks the 3ʹ-5ʹ- phosphodiester linkages in a bimolecular fashion to form linearized pentavalent phosphorus intermediates, which would then collapse and disproportionate the phosphate groups to either the 3ʹ- or 5ʹ-ends of the fragments (see FIG.1B). Thus, in transesterification reactions resulting in strand scission, the phosphate groups always reside at the 3’-ends, while in hydrolysis reactions, the phosphate groups can reside at both the 5’-ends and the 3’-ends. The degradation of mRNA was studied for LNP formulations with two different types of mRNA (one that encodes a first viral antigen and one that encodes for a second different viral antigen), to demonstrate that the mechanism of degradation is independent of sequence. This was studied using a 3ʹ-RACE +/- PNK workflow (3ʹ-rapid amplification of cDNA ends +/- polynucleotide kinase), which allowed for rapid profiling of the 3ʹ-end sites. mRNA fragments were ligated with a sequence-defined, 5ʹ-adenylated DNA adaptor oligonucleotide at their 3ʹ- ends using thermostable T4 ligase; the ligated DNA-RNA hybrid strands were then subjected to library prep and NGS sequencing on a MiSeq (Illumina). It should be noted that this workflow only applies to mRNA fragments that are 3ʹ- terminated as hydroxyl groups. If the mRNA fragments are 3ʹ-phosphate protected – as in the case of transesterification-derived fragments – these phosphates must be cleaved prior to sequencing. In this example, this was achieved by incorporating a polynucleotide kinase (PNK)- mediated phosphate removal step. Thus, by comparing the number of sequencing reads in PNK- treated vs. non-PNK-treated samples, it could be determined whether the 3ʹ-termini of RNA fragments were phosphorylated or remained as hydroxyls. If transesterification were the major strand cleavage mechanism, the 3ʹ-termini of RNA fragments would be expected to be primarily phosphorylated, and it would be expected to (1) detect a lot more sequence reads in the PNK-treated sample than in the non-PNK-treated samples, and (2) detect minimal sequence reads in the non-PNK-treated samples. On the other hand, if hydrolysis were the major strand cleavage mechanism, the backbone phosphate groups would be expected to be disproportioned to either the 5ʹ- or 3ʹ-end of the fragments, and hence some portion of fragment 3ʹ-termini would be expected to remain as unphosphorylated 3ʹ- hydroxyls. Thus, it would be expected to detect some abundance of sequencing reads in the non- PNK-treated samples as well. Liquid LNP formulations were analyzed after storage for 3 months at 5 °C, as shown in FIG.2A (a formulation comprising mRNA that encodes a viral antigen) and FIG.2B (a formulation comprising mRNA that encodes a different viral antigen). The X-axis denotes the position at which RNA fragment ligation to the sequence-defined DNA adaptor occurred, which is in turn indicative of the 3ʹ-ends of the RNA fragments. The Y-axis corresponds to the number of detected sequence reads that have 3ʹ-ends corresponding to the respective nucleotide. In both FIG.2A and 2B, which show with PNK and without PNK, sequence reads were detected almost exclusively in the PNK-treated samples, and very little sequence reads were detected in the non- PNK-treated samples except for the full-length product (which is hydroxyl-terminated). This observation suggested that most RNA fragments had 3ʹ-ends that were phosphorylated, and very few fragments were 3ʹ-terminated as unprotected hydroxyls. These findings indicate that both mRNAs underwent strand scission by a transesterification mechanism, and this this is the predominant mechanism of degradation of mRNA regardless of sequence. EXAMPLE 2 This example describes the relationship between degradation of mRNA and the number of nucleotides of the mRNA. This example demonstrates that the percentage of degraded mRNA generally increases as the number of nucleotides in the mRNA increases. As demonstrated in Example 1, mRNA degradation predominantly takes place via transesterification resulting in an integral full-length parent mRNA breaking into smaller fragments. Transesterification is a random event and can occur at any site along the mRNA backbone. Therefore, relative to shorter mRNAs, longer mRNAs have a higher probability of incurring strand breakage and are mechanistically predicted to degrade faster. Six formulations with mRNAs with different numbers of nucleotides (i.e., 659, 785, 914, 1,106, 2,498, and 2,993 nucleotides) were monitored by a size-based RP-HPLC purity method over 14 days stored at 40 °C (see FIG.3). FIG.3 demonstrates that the percentage of degraded mRNA generally increased as the number of nucleotides in the mRNA increased. Without wishing to be bound by theory, it is believed that, if discrepancies are observed, they could be due to co-elution of some longer mRNA fragments with the integral full-length mRNA in some instances. Nevertheless, overall, the data demonstrate that the percentage of degraded mRNA generally increases as the number of nucleotides in the mRNA increases. EXAMPLE 3 This example describes the amount of degradation observed when an LNP formulation comprising mRNA (that has over 4,000 nucleotides) is stored at 5 °C and -70 °C. As shown in FIG.4, the degradation of the mRNA was higher at 5 °C than at -70 °C. As shown in FIG.4, the degradation rate at 5 °C was determined to be approximately 8% degradation per month at 5 °C. EXAMPLE 4 This example evaluates the in vivo response of an LNP formulation comprising mRNA (that encodes a viral antigen) after partial degradation due to simulation of long term storage via application of heat. 12 female 8-week old BALB/C mice were injected on day 1 and day 22 with 2 µg of the same LNP formulations with various amounts of degradation. The formulations had been treated with heat to simulate various amounts of time stored at 5 °C: 0 months (76% mRNA purity), 4 months (71% mRNA purity), 14 months (61% mRNA purity), and 26 months (49% mRNA purity). As shown in FIG.5, the geometric mean titers produced in the subjects decreased linearly with decreasing purity. This demonstrates that the purity of the mRNA may affect the geometric mean titers produced in the subject. EXAMPLE 5 This example describes the balance between stability of an article and commercial supply of the article. Pharmaceutical products, including vaccines, degrade over time, which ultimately results in a loss of activity. An understanding of the mechanisms of product degradation is critical to managing the overall shelf-life of the product. The proposed storage of the product is -70°C to maximize product shelf-life, however it is understood that this may not be suitable for commercialization and supply in certain geographical regions particularly in lower middle, or lower income countries where cold-chain storage and supply is challenging. An alternative was developed in which shelf life is managed through the determination of the minimum potency requirement (minimum effective dose), determination of the degradation rate, and then provision of additional product in the vial to account for degradation at higher storage temperatures. The exact amount included will be dependent upon the final dose selected in clinical trials, and the amount of time required at non- frozen storage conditions. It is expected that the selected dose will be sufficiently low, such that the inclusion of additional drug in the vial will not significantly impact cost or manufacturing complexity. This provides significant supply chain and storage flexibility for the product, which includes a stable product at -70°C combined with the opportunity to include additional material to permit storage at 5°C, nominally for 3 months, which is consistent with industry expectations for vaccines, including in lower income countries. A driver towards a commercially acceptable vaccine product is the alignment of the overall product stability and shelf-life at the intended storage condition with the requirements of manufacturing, distribution and administration of the product. For many vaccines, particularly those utilizing live attenuated viral vectors, degradation of the product upon storage is expected, even when stored frozen. Similarly, for all nucleic-acid based vaccines, some degradation of the product during storage is expected, particularly at elevated temperatures. This degradation however is not expected to be limiting to the commercial suitability or utility of the proposed vaccine. Fundamental characterization of product degradation, as described in Example 1, has driven a mechanistic understanding which has ultimately led to process improvements and tighter product control. Broadly speaking, the mechanisms of degradation in the lipid nanoparticle (LNP)-mRNA products can be categorized as either being driven by physical (e.g. particle integrity) or chemical (mRNA strand integrity or lipid degradation) processes. As for many biological products, there are a number of critical quality (analytical) attributes for the product, and by extension a number of these are considered to be limiting for the product if they drop below a specified threshold. The advances in process and storage understanding resulted in a particle that is generally physically stable, however storage around the glass transition (e.g., - 20°C to -40°C) of the product may increase physical instability. The main limiting factor for stability of the vaccine has been determined to be due to chemical degradation, specifically breakage of the mRNA strands in an aqueous environment. Through a series of detailed studies (see Example 1), it was determined that this degradation is driven by a transesterification reaction. The approach to determining shelf-life of the product was therefore based on the mRNA construct purity. As full-length mRNA is required for activity, degradation/breakage of the mRNA strand will render it inactive. The rate of mRNA degradation was dependent upon temperature, as shown in FIG.4, the vaccine product showed negligible product degradation at -70°C, which provides flexibility in manufacturing. This allows for use of bulk freezing technology, for example, for storage of materials prior to vial filling. At 5°C, mRNA degradation was observed as shown in FIG.4. As -70°C may not be preferred as a commercial storage or distribution condition, particularly in regions with limited cold-chain (frozen) infrastructure and depot storage, refrigerated (5°C) cold-chain supply is likely to be preferred. The rate of degradation of mRNA will be used to determine the effective amount of vaccine required in the product. This will be achieved in clinical studies in which both the dose required to engender the desired immunological response, and the overall safety profile will be assessed. The approach therefore is to provide additional material in the vials by increasing vial mRNA content (µg) to account for degradation. A schematic of the product degradation/shelf life and additional content considerations is shown in FIG.6. It is likely that the vaccine product will require a dose below 200 micrograms, permitting additional material to be included without significantly impacting the commercial suitability of the product. The upper dose that can be selected will be determined from the safety data obtained during ongoing clinical studies. The non-lyophilized product and mRNA-LNP platform are suitable for commercialization and supply in real-world situations, particularly in lower middle, or lower income countries where cold-chain storage and supply (including at health care provider premises) may not be robust. As it is probable that the minimum effective dose will be less than 200µg and possibly less than 100µg (data pending), additional material included in the drug product vial will be possible and will permit flexibility in supply, an appropriate shelf-life, and last-mile storage and supply of the product. This product has significant supply chain and storage flexibility, namely a stable product at -70°C combined with the opportunity to include additional material to permit storage at 5°C , nominally for 3 months, which is consistent with industry expectations for vaccines. EXAMPLE 6 This example demonstrates the determination of the glass transition temperature of several compositions comprising mRNA in lipid nanoparticles with varying levels of Tris and sucrose. As described above, the glass transition temperature is the temperature at which an amorphous substance (e.g., sucrose) transitions from a hard and relatively brittle (“glassy”) state into a rubbery or viscous state. Without wishing to be bound by theory, it is believed that product stability is well maintained in the vitrified state as product mobility that may generate deleterious chemical reactions or aggregation events are essentially ceased. The glass transition temperature (Tg’) of compositions were measured by modulated Differential Scanning Calorimetry (mDSC). Tg’ was measured using the reversing heat flow to isolate the Tg’ from non-reversing events, such as crystalline melts and enthalpic relaxations / reorganizations caused by disordered freezing. As shown in Table 2, as the relative concentration of Tris to sucrose increased in the compositions, the Tg’ decreased. Table 2. Measured Tg’ for Tris-Sucrose Systems EXAMPLE 7 This prophetic example demonstrates a method of filling an article, in accordance with certain embodiments. A nucleic acid (e.g., mRNA) is combined with a lipid carrier (e.g., LNP) to form an amount of a liquid pharmaceutical composition in an article (e.g., a vial), wherein the nucleic acid (e.g., mRNA) is formulated in the lipid carrier (e.g., LNP). The amount of liquid pharmaceutical composition in the article is demonstrated in Table 3. The fourth and fifth columns of Table 3 are appropriate for various combinations of shelf- life and degradation rate. For example, the fourth column of Table 3 is appropriate for an article with a 3 month shelf-life (e.g., at 5 °C) and a degradation rate of ~8.3% per month. Similarly, the fourth column of Table 3 would also be appropriate for an article with a 2 month shelf-life and a degradation rate of 12.5% per month, or an article with a 6 month shelf-life and a degradation rate of ~4.1% per month. Similarly, the fifth column of Table 3 is appropriate for an article with a 3 month shelf- life (e.g., at 5 °C) and a degradation rate of 10% per month, as well as an article with a 2 month shelf-life and a degradation rate of 15% per month, or an article with a 6 month shelf-life and a degradation rate of 5% per month. Table 3. Liquid Pharmaceutical Composition Amounts in Articles
EXAMPLE 8 This example demonstrates that, in some instances, mRNA vaccines are effective at low purity levels. The purity of mRNA (i.e., that has over 4,000 nucleotides) in 15,000 vaccine doses (each with 100 micrograms of mRNA) was determined. After this determination was made, the 15,000 doses were kept in the refrigerator (approximately 5 ℃) for various periods of time (up to approximately 85 days) before administration to human subjects. The rate of degradation for this mRNA under these conditions was determined. The percentage purity of the mRNA at the time of administration was calculated based on the initial measured purity, the amount of time each dose was kept in the refrigerator, and the determined rate of degradation under those conditions. The y-axis of FIG.7 shows the calculated purity when removed from the refrigerator (which, in this case, was also the time of administration). As shown in FIG.7, doses ranging from under 55% projected purity to over 77% projected purity were administered to human subjects on day 1, and then doses that again ranged from under 55% projected purity to 77% or higher projected purity were administered to the same human subjects on day 29. Further, it was determined that the efficacy of the vaccine was not directly related to purity alone, but instead was directly related to the amount of intact mRNA administered. For example, a 50 microgram dose of mRNA with 100% intact mRNA (or 100% purity) would provide 50 micrograms of intact mRNA while a 100 microgram dose of mRNA with 50% intact mRNA (or 50% purity) would also provide 50 micrograms of intact mRNA, and both would provide a similar immune response since they have the same amount of intact mRNA. This relationship was further explored by increasing the total amount of mRNA administered and decreasing the purity (e.g., to 46%, 30%, and 18% purity). It was determined that equivalent immune responses could be achieved with vaccines with these lower purities when the total amount of mRNA was increased, such that the total amount of intact mRNA delivered was equivalent. Thus, this example demonstrates that it is the amount of intact mRNA administered that affected the efficacy of the studied mRNA vaccine rather than the purity of the mRNA. EXAMPLE 9 This example studied the minimum amount of intact mRNA needed to ensure effective vaccination of human subjects in order to determine the shelf-life of the vaccine and/or the starting mRNA purity needed to ensure that at least the minimum amount of intact mRNA would be administered throughout the shelf-life of the vaccine. Multiple amounts of intact mRNA were administered to human subjects and the efficacy of the vaccine was studied. It was determined that the efficacy of the vaccine plateaued as the amount of intact mRNA increased, such that there was no observed benefit for efficacy of increasing the amount of intact mRNA beyond the plateau amount. Accordingly, for purposes of this example, it was determined that at least this plateau amount of intact mRNA should be delivered in each dose throughout the shelf-life of the vaccine to ensure no variations in vaccine efficacy. Accordingly, the shelf-life of the vaccine was determined for individual samples taking into consideration the starting mRNA purity, the rate of degradation of the mRNA in specific storage conditions, and the plateau amount of intact mRNA. From this, a general shelf-life for the vaccine was established. Once the general shelf-life was established, the minimum starting mRNA purity needed in the vaccine was determined by taking into consideration the shelf-life, the rate of degradation of the mRNA in specific storage conditions, and the plateau amount of intact mRNA. It was determined that the presence of degraded mRNA did not affect safety or efficacy of the vaccine. Thus, this example demonstrates how the starting mRNA purity, the shelf-life of the vaccine, and the final amount of intact mRNA (e.g., the plateau amount) interact with one another. For example, it was determined that to extend the shelf-life (or include storage conditions where degradation is accelerated), the plateau amount of intact mRNA could still be administered at any point throughout the shelf-life if the mRNA purity in the starting product was increased. EQUIVALENTS While several inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the function and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the inventive teachings is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, inventive embodiments may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the inventive scope of the present disclosure. All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms. All references, patents and patent applications disclosed herein are incorporated by reference with respect to the subject matter for which each is cited, which in some cases may encompass the entirety of the document. The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.” The phrase “and/or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and/or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and/or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and/or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc. As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and/or” as defined above. For example, when separating items in a list, “or” or “and/or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law. As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and/or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc. Each possibility represents a separate embodiment of the present invention. It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited. In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i. ., to mean including but not limited to. Only the transitional phrases “consisting of” and “consisting essentially of” shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.