pH-sensitive, cationic liposomes: a new synthetic virus-like vector.
We describe the use of cationic, pH-sensitive liposomes to mediate the efficient transfer of DNA into a variety of cells in culture. Cationic lipids, containing an amine with a pK within the physiologic range of 4.5 to 8, were synthesized and incorporated with dioleoylphosphatidylethanolamine into liposomes. Acid conditions promoted DNA-binding, DNA-incorporation, and DNA-induced fusion by these cationic, pH-sensitive liposomes. Transfection efficiency in cultured cells was dependent on endosomal acidification in a manner akin to acidic-induced endosomal release of viruses. These liposomes constitute a promising new class of reagents for gene therapy.
Budker
V
V
Department of Pediatrics, Waisman Center, University of Wisconsin, Madison 53705, USA.
Gurevich
V
V
Hagstrom
J E
JE
Bortzov
F
F
Wolff
J A
JA
D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020126:Brefeldin A; D002412:Cations; D002738:Chloroquine / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D011992:Endosomes / Q000187:drug effects; D005822:Genetic Vectors; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D018942:Macrolides; D051379:Mice; D014162:Transfection / Q000379:methods*
D000900:Anti-Bacterial Agents; D002412:Cations; D003517:Cyclopentanes; D008081:Liposomes; D018942:Macrolides; D020126:Brefeldin A; D002738:Chloroquine; C040929:bafilomycin A1