Poster abstracts
Poster number 3 submitted by Kaizheng Liu
A New "On/Off Switch" for RNA: Reversible Acylation Responsive to Esterases
Kaizheng Liu (Department of Chemistry, Carnegie Mellon University), Anna M Kietrys (Department of Chemistry, Carnegie Mellon University)
Abstract:
We have developed a strategy for controlling RNA function via the reversible acylation of its 2′-hydroxyl group. Our novel acylating reagent, EST1A, circumvented the need for toxic chemicals in the deacylation step; instead, the acyl group was enzymatically cleaved by endogenous esterases. After validating the reversibility on oligonucleotides, we applied it to both eGFP mRNA and siRNA. Notably, this modification led to a significant enhancement of siRNA-mediated gene knockdown. Functional assays with acylated eGFP mRNA in HepG2 and U87MG cells confirmed that deacylation is mediated by both carboxylesterases and cholinesterases in cellulo. By harnessing the differential expression of esterases across cell lines, this non-toxic strategy establishes a generalizable platform for spatiotemporal control of RNA function and opens a path toward cell-selective RNA therapeutics.
References:
K. Liu and A. M. Kietrys, bioRxiv, 2024, DOI: 10.1101/2024.08.29.610419, 2024.2008.2029.610419.
Keywords: Reversible RNA acylation, Esterase-mediated deprotection, Cell-selective RNA therapeutics