Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1371022 | Bioorganic & Medicinal Chemistry Letters | 2015 | 4 Pages |
Abstract
We evaluated the effect of combining 2′-O-[2-[2-(N,N-dimethylamino)ethoxy]ethyl] (2′-O-DMAEOE), a 2′-cationic modification, with a 2′,4′-constrained 2′-O-ethyl nucleic acid (cEt BNA) on the activity of an antisense oligonucleotide (ASO) using PTEN as a model target. Our results suggest that replacing one cEt BNA nucleotide with 2′-O-DMAEOE nucleotide at the 5′-end of a 2-10-2 gapmer ASO maintained the potency relative to parent ASO in liver. The cationic 2′-O-DMAEOE modification did not improve the activity of ASO in extra-hepatic tissues. Results from this study provide guidance to design improved antisense oligonucleotide drugs.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Sanjay K. Pandey, Anna Nowak, Jake Perkins, Annie Ferng, Thazha P. Prakash,