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Cholesterol-modified anti-MDR1 small interfering RNA: Uptake and biological activity

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Abstract

Small interfering RNAs (siRNA) are considered to be potential agents for specific gene silencing, but low the efficacy of siRNA delivery into cells limits their biomedical application. Accumulation of siRNA coupled with cholesterol residue at the 5′-end of the “sense” strand (chol-siRNA) was studied in HEK293, HepG2, SC1, and KB-8-5 cells. In the absence of a transfection agent, the levels of both carrier-free and chol-siRNAs were very low, whereas transfection agent substantially increased transfection rate in all cell lines; in HEK293, SC1, and KB-8-5 cells transfection efficiency of the chol-siRNA was higher than that of the corresponding unmodified siRNA. Biological activity of anti-MDR1-siRNAs targeted to the 557–577 nt region of the MDR1 gene mRNA was estimated as multiple drug resistance phenotype reverting activity of KB-8-5 cancer cells. The chol-siRNA induced cancer cells’ death in the presence of previously tolerated vinblastine doses more effectively than unmodified siRNA.

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Abbreviations

C :

2′-O-methyl-cytosine

U :

2′-O-methyl-uridine

chol:

cholesterol residue

siRNA:

small interfering RNA

LDL:

low-density lipoproteins

MDR:

multiple drug resistance

MTT:

3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide

FBS:

fetal bovine serum

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Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    N. S. Kruglova, M. I. Meschaninova, A. G. Venyaminova, M. A. Zenkova, V. V. Vlassov & E. L. Chernolovskaya

Authors
  1. N. S. Kruglova
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  2. M. I. Meschaninova
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  3. A. G. Venyaminova
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  4. M. A. Zenkova
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  5. V. V. Vlassov
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  6. E. L. Chernolovskaya
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Corresponding author

Correspondence to E. L. Chernolovskaya.

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Original Russian Text © N.S. Kruglova, M.I. Meschaninova, A.G. Venyaminova, M.A. Zenkova, V.V. Vlassov, E.L. Chernolovskaya, 2010, published in Molekulyarnaya Biologiya, 2010, Vol. 44, No. 2, pp. 284–293.

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Kruglova, N.S., Meschaninova, M.I., Venyaminova, A.G. et al. Cholesterol-modified anti-MDR1 small interfering RNA: Uptake and biological activity. Mol Biol 44, 254–261 (2010). https://doi.org/10.1134/S002689331002010X

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  • DOI: https://doi.org/10.1134/S002689331002010X

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