Robust, Durable Gene Activation In Vivo via mRNA-Encoded Activators.
ACS Nano
; 16(4): 5660-5671, 2022 04 26.
Article
em En
| MEDLINE
| ID: mdl-35357116
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Sistemas CRISPR-Cas
/
Lipossomos
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article