4′-Guanidinium-modified siRNA: a molecular tool to control RNAi activity through RISC priming and selective antisense strand loading

Ganesh N. Nawale; Saeed Bahadorikhalili; Pallabi Sengupta; Sandeep Kadekar; Subhrangsu Chatterjee; Oommen P. Varghese

doi:10.1039/C9CC04141A

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4′-Guanidinium-modified siRNA: a molecular tool to control RNAi activity through RISC priming and selective antisense strand loading†

Ganesh N. Nawale,

^a Saeed Bahadorikhalili,^a Pallabi Sengupta,^b Sandeep Kadekar,^a Subhrangsu Chatterjee^b and Oommen P. Varghese

*^a

Author affiliations

* Corresponding authors

^a Translational Chemical Biology Laboratory, Division of Polymer Chemistry, Department of Chemistry-Ångström, Uppsala University, Uppsala, Sweden
E-mail: oommen.varghese@kemi.uu.se

^b Biomolecular NMR and Drug Design Laboratory, Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata, India

Abstract

We designed novel 4′-C-guanidinocarbohydrazidomethyl-5-methyl uridine (GMU) modified small interfering RNA (siRNA) and evaluated its biophysical and biochemical properties. Incorporation of GMU units significantly increased the thermodynamic stability as well as the enzymatic stability against nucleases in human serum. A gene silencing experiment indicated that GMU modfied siRNA (siRNA6) resulted in ≈4.9-fold more efficient knockdown than unmodified siRNA.

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DOI: https://doi.org/10.1039/C9CC04141A
Article type: Communication
Submitted: 29 May 2019
Accepted: 05 Jul 2019
First published: 05 Jul 2019
This article is Open Access

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Chem. Commun., 2019,55, 9112-9115

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4′-Guanidinium-modified siRNA: a molecular tool to control RNAi activity through RISC priming and selective antisense strand loading

G. N. Nawale, S. Bahadorikhalili, P. Sengupta, S. Kadekar, S. Chatterjee and O. P. Varghese, Chem. Commun., 2019, 55, 9112 DOI: 10.1039/C9CC04141A

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Chemical Communications

4′-Guanidinium-modified siRNA: a molecular tool to control RNAi activity through RISC priming and selective antisense strand loading†

Abstract

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Supplementary files

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4′-Guanidinium-modified siRNA: a molecular tool to control RNAi activity through RISC priming and selective antisense strand loading

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