Abstract:
:Technologies allowing for specific regulation of endogenous genes are valuable for the study of gene functions and have great potential in therapeutics. We created the CRISPR-on system, a two-component transcriptional activator consisting of a nuclease-dead Cas9 (dCas9) protein fused with a transcriptional activation domain and single guide RNAs (sgRNAs) with complementary sequence to gene promoters. We demonstrate that CRISPR-on can efficiently activate exogenous reporter genes in both human and mouse cells in a tunable manner. In addition, we show that robust reporter gene activation in vivo can be achieved by injecting the system components into mouse zygotes. Furthermore, we show that CRISPR-on can activate the endogenous IL1RN, SOX2, and OCT4 genes. The most efficient gene activation was achieved by clusters of 3-4 sgRNAs binding to the proximal promoters, suggesting their synergistic action in gene induction. Significantly, when sgRNAs targeting multiple genes were simultaneously introduced into cells, robust multiplexed endogenous gene activation was achieved. Genome-wide expression profiling demonstrated high specificity of the system.
journal_name
Cell Resjournal_title
Cell researchauthors
Cheng AW,Wang H,Yang H,Shi L,Katz Y,Theunissen TW,Rangarajan S,Shivalila CS,Dadon DB,Jaenisch Rdoi
10.1038/cr.2013.122subject
Has Abstractpub_date
2013-10-01 00:00:00pages
1163-71issue
10eissn
1001-0602issn
1748-7838pii
cr2013122journal_volume
23pub_type
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