Bait-and-Switch Supramolecular Strategy To Generate Noncationic RNA-Polymer Complexes for RNA Delivery.

Abstract:

:RNA interference (RNAi) requires the intracellular delivery of RNA molecules to initiate the neutralization of targeted mRNA molecules, inhibiting the expression or translation of the targeted gene. Current polymers and lipids that are used to deliver RNA molecules are generally required to be positively charged, to achieve complexation with RNA and the cellular internalization. However, positive surface charge has been implicated as the reason for toxicity in many of these systems. Herein, we report a novel strategy to generate noncationic RNA-polymer complexes for RNA delivery with low cytotoxicity. We use an in situ electrostatic complexation using a methylated pyridinium group, which is simultaneously removed during the RNA binding step. The resultant complexes demonstrate successful knockdown in preimplantation mammalian embryos, thus providing a new approach for nucleic acid delivery.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Jiang Z,Cui W,Prasad P,Touve MA,Gianneschi NC,Mager J,Thayumanavan S

doi

10.1021/acs.biomac.8b01321

subject

Has Abstract

pub_date

2019-01-14 00:00:00

pages

435-442

issue

1

eissn

1525-7797

issn

1526-4602

journal_volume

20

pub_type

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