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Volume 22
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Article

An Influence of Modification with Phosphoryl Guanidine Combined with a 2′-O-Methyl or 2′-Fluoro Group on the Small-Interfering-RNA Effect

by
Anna S. Pavlova
,
Kristina I. Yakovleva
,
Anna V. Epanchitseva
,
Maxim S. Kupryushkin
,
Inna A. Pyshnaya
,
Dmitrii V. Pyshnyi
,
Elena I. Ryabchikova
* and
Ilya S. Dovydenko
*
Institute of Chemical Biology and Fundamental Medicine (ICBFM), Siberian Branch of Russian Academy of Sciences (SB RAS), 630090 Novosibirsk, Russia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(18), 9784; https://doi.org/10.3390/ijms22189784
Submission received: 16 July 2021 / Revised: 30 August 2021 / Accepted: 8 September 2021 / Published: 10 September 2021
(This article belongs to the Special Issue Precision Nucleic Acid Therapeutics)
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Abstract

Small interfering RNA (siRNA) is the most important tool for the manipulation of mRNA expression and needs protection from intracellular nucleases when delivered into the cell. In this work, we examined the effects of siRNA modification with the phosphoryl guanidine (PG) group, which, as shown earlier, makes oligodeoxynucleotides resistant to snake venom phosphodiesterase. We obtained a set of siRNAs containing combined modifications PG/2′-O-methyl (2′-OMe) or PG/2′-fluoro (2′-F); biophysical and biochemical properties were characterized for each duplex. We used the UV-melting approach to estimate the thermostability of the duplexes and RNAse A degradation assays to determine their stability. The ability to induce silencing was tested in cultured cells stably expressing green fluorescent protein. The introduction of the PG group as a rule decreased the thermodynamic stability of siRNA. At the same time, the siRNAs carrying PG groups showed increased resistance to RNase A. A gene silencing experiment indicated that the PG-modified siRNA retained its activity if the modifications were introduced into the passenger strand.
Keywords: modified siRNA; phosphoryl guanidine group; RNA interference modified siRNA; phosphoryl guanidine group; RNA interference
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MDPI and ACS Style

Pavlova, A.S.; Yakovleva, K.I.; Epanchitseva, A.V.; Kupryushkin, M.S.; Pyshnaya, I.A.; Pyshnyi, D.V.; Ryabchikova, E.I.; Dovydenko, I.S. An Influence of Modification with Phosphoryl Guanidine Combined with a 2′-O-Methyl or 2′-Fluoro Group on the Small-Interfering-RNA Effect. Int. J. Mol. Sci. 2021, 22, 9784. https://doi.org/10.3390/ijms22189784

AMA Style

Pavlova AS, Yakovleva KI, Epanchitseva AV, Kupryushkin MS, Pyshnaya IA, Pyshnyi DV, Ryabchikova EI, Dovydenko IS. An Influence of Modification with Phosphoryl Guanidine Combined with a 2′-O-Methyl or 2′-Fluoro Group on the Small-Interfering-RNA Effect. International Journal of Molecular Sciences. 2021; 22(18):9784. https://doi.org/10.3390/ijms22189784

Chicago/Turabian Style

Pavlova, Anna S., Kristina I. Yakovleva, Anna V. Epanchitseva, Maxim S. Kupryushkin, Inna A. Pyshnaya, Dmitrii V. Pyshnyi, Elena I. Ryabchikova, and Ilya S. Dovydenko. 2021. "An Influence of Modification with Phosphoryl Guanidine Combined with a 2′-O-Methyl or 2′-Fluoro Group on the Small-Interfering-RNA Effect" International Journal of Molecular Sciences 22, no. 18: 9784. https://doi.org/10.3390/ijms22189784

APA Style

Pavlova, A. S., Yakovleva, K. I., Epanchitseva, A. V., Kupryushkin, M. S., Pyshnaya, I. A., Pyshnyi, D. V., Ryabchikova, E. I., & Dovydenko, I. S. (2021). An Influence of Modification with Phosphoryl Guanidine Combined with a 2′-O-Methyl or 2′-Fluoro Group on the Small-Interfering-RNA Effect. International Journal of Molecular Sciences, 22(18), 9784. https://doi.org/10.3390/ijms22189784

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