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Overcoming GNA/RNA Base-Pairing Limitations Using Isonucleotides Improves the Pharmacodynamic Activity of ESC+ GalNAc-siRNAs

ABSTRACT: We report the impact of two pairs of GNA nucleotides, the native GNA-C and -G compared with the isomeric GNA-isoC and -isoG, on the on- and off-target activity of chemically modified siRNAs in primary mouse hepatocytes by RNA sequencing. We found that both GNA-C and -isoC mitigate the suppression of off-targets in a similar fashion, however, GNA-isoG was less efficacious in the mitigation of off-targets as the native GNA-G. This study informs the further design of more potent and specific chemically modified siRNAs for potential application in RNAi therapeutics.

ORGANISM(S): Mus musculus

PROVIDER: GSE183164 | GEO | 2021/09/24

REPOSITORIES: GEO

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Overcoming GNA/RNA base-pairing limitations using isonucleotides improves the pharmacodynamic activity of ESC+ GalNAc-siRNAs.

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