In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR–dCas9-activator transgenic mice
Authors:
- 15 January 2018
- journal article
- research article
- Published by Springer Nature in Nature Neuroscience
- Vol. 21 (3) , 440-446
Abstract
Despite rapid progresses in the genome-editing field, in vivo simultaneous overexpression of multiple genes remains challenging. We generated a transgenic mouse using an improved dCas9 system that enables simultaneous and precise in vivo transcriptional activation of multiple genes and long noncoding RNAs in the nervous system. As proof of concept, we were able to use targeted activation of endogenous neurogenic genes in these transgenic mice to directly and efficiently convert astrocytes into functional neurons in vivo. This system provides a flexible and rapid screening platform for studying complex gene networks and gain-of-function phenotypes in the mammalian brain.Keywords
This publication has 56 references indexed in Scilit:
- Erratum: Corrigendum: Orthogonal gene knockout and activation with a catalytically active Cas9 nucleaseNature Biotechnology, 2016
- Multiplexable, locus-specific targeting of long RNAs with CRISPR-DisplayNature Methods, 2015
- A split-Cas9 architecture for inducible genome editing and transcription modulationNature Biotechnology, 2015
- Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complexNature, 2014
- A Protein-Tagging System for Signal Amplification in Gene Expression and Fluorescence ImagingCell, 2014
- Genome-Scale CRISPR-Mediated Control of Gene Repression and ActivationCell, 2014
- RNA-guided gene activation by CRISPR-Cas9–based transcription factorsNature Methods, 2013
- CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in EukaryotesCell, 2013
- Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene ExpressionCell, 2013
- Effect of Genome Size on AAV Vector PackagingMolecular Therapy, 2010