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

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

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 nuc...

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Veröffentlicht in:Chemical communications (Cambridge, England) England), 2019-07, Vol.55 (62), p.9112-9115
Hauptverfasser: Nawale, Ganesh N, Bahadorikhalili, Saeed, Sengupta, Pallabi, Kadekar, Sandeep, Chatterjee, Subhrangsu, Varghese, Oommen P
Format: Artikel
Sprache:eng
Schlagworte:
Gene expression
Priming
Stability
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Zusammenfassung: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. We present synthesis, biochemical, biophysical and computational evaluation of 4′ gunanidino modified siRNA.
ISSN:1359-7345
1364-548X
1364-548X
DOI:10.1039/c9cc04141a