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
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/S0163-7258(00)00062-0

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.