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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Beyersdorf, JP; Bawage, S; Iglesias, N; Peck, HE; Hobbs, RA; Wroe, JA; Zurla, C; Gersbach, CA; Santangelo, PJ

Published Date

  • April 2022

Published In

Volume / Issue

  • 16 / 4

Start / End Page

  • 5660 - 5671

PubMed ID

  • 35357116

Pubmed Central ID

  • PMC9047660

Electronic International Standard Serial Number (EISSN)

  • 1936-086X

International Standard Serial Number (ISSN)

  • 1936-0851

Digital Object Identifier (DOI)

  • 10.1021/acsnano.1c10631


  • eng