Modified concatemeric oligonucleotide complexes: new system for efficient oligonucleotide transfer into mammalian cells.
Antisense oligonucleotides and double-stranded small interfering RNAs have become an important instrument for the manipulation of gene expression in molecular biology experiments and a promising tool for the development of gene-targeted therapeutics. One of the main impediments in the use of oligonucleotide-based therapeutics is their poor uptake by target cells. The formation of supramolecular concatemeric complexes by oligonucleotides was shown to promote their binding to various mammalian cells [Simonova, O.N.,Vladimirova, A.V., Zenkova, M.A., and Vlassov, V.V. (2006). Biochim. Biophys. Acta 1758, 413-418]. We attempted to improve the efficiency of oligonucleotide concatemer delivery into cells by the attachment of lipophilic cholesterol molecules to the components of concatemeric complexes. Uptake, cellular distribution, and biological activity of the supramolecular complexes formed by delivered antisense oligonucleotides and cholesterol-modified "carrier" oligonucleotides were studied. Our results demonstrate that incorporation of an antisense oligonucleotide into the self-assembling concatemeric system promotes its delivery into cells without the addition of any supplementary transfection agents and allows achieving specific inhibition of the target gene expression.
Gusachenko Simonova
Olesya N
ON
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia. olesya.simonova@niboch.nsc.ru
Pishnyi
Dmitrii V
DV
Vlassov
Valentin V
VV
Zenkova
Marina  A
M
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism*; D006224:Cricetinae; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D007372:Interferons / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
D016376:Oligonucleotides, Antisense; D007372:Interferons; D002784:Cholesterol; D016650:Fluorescein-5-isothiocyanate