1.
Bioorg Med Chem Lett
; 25(8): 1688-1691, 2015 Apr 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-25804718
RESUMO
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.