Synthesis of Novel Cationic Lipids: Effect of Structural Modification on the Efficiency of Gene Transfer
摘要:
A series of novel cationic lipids was designed and synthesized in an effort to understand the importance of the various structural features with respect to transfection efficiency. Particular attention has been paid to the hydrophobic domain and the cationic headgroup. An efficient method of synthesizing asymmetric diether lipids is described, using alkyl chains ranging from C-12 to C-18 and the unsaturated oleyl group. The ternary formulations including the diether lipid 3beta-[N-(N',N'-dimethylaminoethyl)carbamoyl]cholesterol (DC-Chol) and dioleoyl phosphatidylethanolamine (DOPE) were up to 10-fold more efficacious in in vitro assays than the DC-Chol/DOPE control. The shorter and most asymmetric diether lipids performed the best. The chemical nature and basicity of the headgroups have been varied by the coupling of the four naturally occurring amino acids with cationic side chains-arginine, histidine, lysine, and tryptophan. Transfection efficiency was highest for arginine/lysine derivatives, with binary formulations containing the amino acid derivative alone and,DOPE proving superior.
The present invention provides polyoxaline-dialkyloxypropyl conjugates (POZ-DAA), SNALP compositions comprising POZ-DAA conjugates and methods of using such SNALP compositions to introduce a therapeutic agent, such as a nucleic acid, into a cell (e.g., for the treatment of a disease or disorder).
Polyethyleneglycol-modified lipid compounds and uses thereof
申请人:Heyes James
公开号:US20050175682A1
公开(公告)日:2005-08-11
The present invention provides compositions comprising polytheylyene-dialkyloxypropyl conjugates (PEG-DAA), liposomes, SNALP, and SPLP comprising such compositions, and methods of using such compositions, liposomes, SNALP, and SPLP.
The present invention provides compositions and methods for silencing gene expression by delivering nucleic acid-lipid particles comprising a siRNA molecule to a cell.
POLYETHYLENEGLYCOL-MODIFIED LIPID COMPOUNDS AND USES THEREOF
申请人:Heyes James
公开号:US20110091525A1
公开(公告)日:2011-04-21
The present invention provides compositions comprising polytheylyene-dialkyloxypropyl conjugates (PEG-DAA), liposomes, SNALP, and SPLP comprising such compositions, and methods of using such compositions, liposomes, SNALP, and SPLP.