Robust, Durable Gene Activation In Vivo via mRNA-Encoded Activators.

TitleRobust, Durable Gene Activation In Vivo via mRNA-Encoded Activators.
Publication TypeJournal Article
Year of Publication2022
AuthorsJP Beyersdorf, S Bawage, N Iglesias, HE Peck, RA Hobbs, JA Wroe, C Zurla, CA Gersbach, and PJ Santangelo
JournalAcs Nano
Start Page5660
Pagination5660 - 5671
Date Published04/2022

Programmable control of gene expression via nuclease-null Cas9 fusion proteins has enabled the engineering of cellular behaviors. Here, both transcriptional and epigenetic gene activation via synthetic mRNA and lipid nanoparticle delivery was demonstrated in vivo. These highly efficient delivery strategies resulted in high levels of activation in multiple tissues. Finally, we demonstrate durable gene activation in vivo via transient delivery of a single dose of a gene activator that combines VP64, p65, and HSF1 with a SWI/SNF chromatin remodeling complex component SS18, representing an important step toward gene-activation-based therapeutics. This induced sustained gene activation could be inhibited via mRNA-encoded AcrIIA4, further improving the safety profile of this approach.

Short TitleAcs Nano