Delivery systems for antisense oligonucleotides

• Published in: Pharmacology & therapeutics (Oxford) Vol. 87; no. 2; pp. 255 - 277
• Main Authors: Garcia-Chaumont, Ch, Seksek, O, Grzybowska, J, Borowski, E, Bolard, J
• Format: Book Review Journal Article
• Language: English
• Published: England Elsevier Inc 01.08.2000
• Subjects: Amphotericin B; Amphotericin B - metabolism; Antisense; Cationic lipids; Cell Membrane - physiology; Drug Delivery Systems; Endocytosis; Gene therapy; Genetic Therapy; Humans; Liposomes; Micelles; Oligonucleotides; Oligonucleotides, Antisense - administration & dosage; Permeability; EGF, epidermal growth factor; DOGS, dioctadecylamidoglycylspermine; DOPE, 1,2-dioleoyl- sn-glycero-3-phosphatidylethanolamine; DMEM, Dulbecco's modified Eagle medium; OA, oleic acid; PS-ODN, phosphorothioate oligodeoxyribonucleotide; HVJ, hemagglutinating virus of Japan; OAMA, N- d-ornithylamphotericin B 3′-dimethylaminopropyl amide; CHEMS, cholesterylhemisuccinate; LUV, large unilamellar vesicles; AS-ODN, antisense oligodeoxyribonucleotide; MDR, multidrug-resistant; DIP, N-dodecyl imidazole propionate; TMAG, N-(α-trimethylammonioacetyl)-didodecyl- d-glutamate chloride; HIV, human immunodeficiency virus; Cationic lipids; EPC, egg yolk phosphatidylcholine; PE, phosphatidylethanolamine; DOTMA, N-[1-(2,3-dioleoxy)propyl]- n,n,n-trimethylammonium chloride; DEAE, diethylaminoethyl; ODN, oligodeoxyribonucleotide; Gene therapy; DOTAP, 1,2-bis-(oleoyloxy)-3-(trimethylammonium)propane; DOSPA, 2,3-dioleoyloxy- N-[2(sperminecarboxamido)ethyl]- N,N-dimethyl-1-propanaminium trifluoroacetate; Oligonucleotides; Antisense; PAMAM, polyamidoamine; DC-Chol, 3β[ N-( N′, N′-dimethylaminoethane)carbamoyl] cholesterol; DMRIE, dimyristooxypropyl dimethyl hydroxyethyl ammonium bromide; pLK, poly( l-lysine); AsOR, asialoorosomucoid; DOIC, 1-[2-(oleoyloxy)-ethyl]-2-oleoyl-3-(2-hydroxyethyl)imidazolinium chloride; GUV, giant unilamellar vesicles; HII, inverted hexagonal phases; LDL, low-density lipoprotein; ICAM, intracellular adhesion molecule; BSA, bovine serum albumin; GFP, green fluorescent protein; PKC, protein kinase C; VSV, vesicular stomatitis virus; DHBV, duck hepatitis B virus; SUV, small unilamellar vesicles; PO-ODN, phosphodiester oligodeoxyribonucleotide; DODAB, dioctadecyl dimethylammonium bromide; PEI, polyethyleneimine; Amphotericin B; CAT, chloramphenicol acetyltransferase; Liposomes; AMA, amphotericin B 3′-dimethylaminopropyl amide
• DOI: 10.1016/S0163-7258(00)00062-0
• ISSN: 0163-7258

In vitro, the efficacy of the antisense approach is strongly increased by systems delivering oligodeoxyribonucleotides (ODNs) to cells. Up to now, most of the developed vectors favor ODN entrance by a mechanism based on endocytosis. Such is the case for particulate systems, including liposomes (cationic or non-cationic), cationic polyelectrolytes, and delivery systems targeted to specific receptors. Under these conditions, endosomal compartments may represent a dead end for ODNs. Current research attempts to develop conditions for escaping from these compartments. A new class of vectors acts by passive permeabilization of the plasma membrane. It includes peptides, streptolysin O, and cationic derivatives of polyene antibiotics. In vivo, the interest of a delivery system, up to now, has appeared limited. Development of vectors insensitive to the presence of serum seems to be a prerequisite for future improvements.