Towards Zwitterionic Oligonucleotides with Improved Properties: the NAA/LNA-Gapmer Approach.

ABSTRACT: Oligonucleotides (ON) are promising therapeutic candidates, for instance by blocking endogenous mRNA (antisense mechanism). However, ON usually require structural modifications of the native nucleic acid backbone to ensure satisfying pharmacokinetic properties. One such strategy to design novel antisense oligonucleotides is to replace native phosphate diester units by positively charged artificial linkages, thus leading to (partially) zwitterionic backbone structures. Herein, we report a "gapmer" architecture comprised of one zwitterionic central segment ("gap") containing nucleosyl amino acid (NAA) modifications and two outer segments of locked nucleic acid (LNA). This NAA/LNA-gapmer approach furnished a partially zwitterionic ON with optimised properties: i) the formation of stable ON-RN

SUBMITTER: Wojtyniak M 

PROVIDER: S-EPMC7754139 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature