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Title:
METHOD OF FORMING PROTEIN-LINKED LIPIDIC MICROPARTICLE, AND COMPOSITION THEREOF
Document Type and Number:
Japanese Patent JP2010031028
Kind Code:
A
Abstract:

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.


Inventors:
PAPAHADJOPOULOS DEMETRIOS
HONG KEELUNG
ZHENG WEIWEN
KIRPOTIN DMITRI
Application Number:
JP2009226639A
Publication Date:
February 12, 2010
Filing Date:
September 30, 2009
Export Citation:
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Assignee:
UNIV CALIFORNIA
International Classes:
C07K17/06; C12N15/09; A61K9/00; A61K9/127; A61K31/7105; A61K31/711; A61K47/10; A61K47/34; A61K47/48; A61K48/00; C07H21/00; C07H21/02; C07H21/04; C12N15/88
Foreign References:
WO1997038731A11997-10-23
WO1996022765A11996-08-01
WO1998016202A21998-04-23
WO1997038731A11997-10-23
Other References:
JPN6012013404; Cancer Research Vol.53, 1993, p.4026-4034
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
Attorney, Agent or Firm:
Atsushi Nakajima
Kato Kazunori
Katsuichi Nishimoto