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Published on: November 26, 2013
Robust, Durable Gene Activation In Vivo via mRNA-Encoded Activators
Jared P Beyersdorf1, Swapnil Bawage1, Nahid Iglesias2
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Krone Engineering Biosystems Building, 950 Atlantic Drive NW, Atlanta, Georgia 30332, United States.
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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