To provide lipid:nucleic acid complexes that have increased shelf life and high transfection activity in vivo following intravenous injection, and to provide methods of preparing such complexes.
The methods generally comprise contacting a nucleic acid with an organic polycation to produce a condensed nucleic acid, and then combining the condensed nucleic acid with a lipid comprising an amphiphilic cationic lipid to produce the lipid:nucleic acid complex. This complex can be further stabilized by the addition of a hydrophilic polymer attached to hydrophobic side chains. This complex can be further stabilized by the addition of a hydrophilic polymer attached to hydrophobic side chains. The complex can also be made specific for specific cells, by incorporating a targeting moiety such as an Fab' fragment attached to a hydrophilic polymer. Further provided are lipidic microparticles with attached proteins which have been conjugated to linker molecules having a hydrophilic polymer domain and a hydrophobic domain capable of stable association with the microparticle, or proteins which have been engineered to contain a hydrophilic domain and a lipid moiety permitting stable association with the microparticle.
HONG KEELUNG
ZHENG WEIWEN
KIRPOTIN DMITRI
WO1997038731A1 | 1997-10-23 | |||
WO1996022765A1 | 1996-08-01 | |||
WO1998016202A2 | 1998-04-23 | |||
WO1997038731A1 | 1997-10-23 |
JPN6012013396; Biochimica et Biophysica Acta Vol.1237, 1995, p.99-108
JPN6012013401; Biochemistry Vol.36, No.1, 1997, p.66-75
JPN6013010992; Bioconjugate Chemistry Vol.8, No.2, 1997, p.111-118
Kato Kazunori
Katsuichi Nishimoto