000			02648nam a2200469Ia 4500
003			MX-MdCICY
005			20250625160158.0
040			_cCICY
090			_aB-16798
245	1	0	_aIn Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation
490	0		_vCell, 171(7), p.1495-1507.e15, 2017
520	3		_aCurrent genome-editing systems generally rely on inducing DNA double-strand breaks (DSBs). This may limit their utility in clinical therapies, as unwanted mutations caused by DSBs can have deleterious effects. CRISPR/Cas9 system has recently been repurposed to enable target gene activation, allowing regulation of endogenous gene expression without creating DSBs. However, in vivo implementation of this gain-of-function system has proven difficult. Here, we report a robust system for in vivo activation of endogenous target genes through trans-epigenetic remodeling. The system relies on recruitment of Cas9 and transcriptional activation complexes to target loci by modified single guide RNAs. As proof-of-concept, we used this technology to treat mouse models of diabetes, muscular dystrophy, and acute kidney disease. Results demonstrate that CRISPR/Cas9-mediated target gene activation can be achieved in vivo, leading to measurable phenotypes and amelioration of disease symptoms. This establishes new avenues for developing targeted epigenetic therapies against human diseases. Video Abstract In vivo delivery of a Cas9-based epigenetic gene activation system ameliorates disease phenotypes in mouse models of type I diabetes, acute kidney injury, and muscular dystrophy
650	1	4	_aCHROMATIN REMODELING
650	1	4	_aCRISPR/CAS9
650	1	4	_aDISEASE MODEL
650	1	4	_aEPIGENETIC MODIFICATION
650	1	4	_aEPIGENETIC THERAPY
650	1	4	_aGENE EDITING
650	1	4	_aMUSCULAR DYSTROPHY
650	1	4	_aREGENERATIVE MEDICINE
650	1	4	_aSTEM CELLS
650	1	4	_aTRANSDIFFERENTIATION
700	1	2	_aLiao, H.-K.
700	1	2	_aHatanaka, F.
700	1	2	_aAraoka, T.
700	1	2	_aReddy, P.
700	1	2	_aWu, M.-Z.
700	1	2	_aSui, Y.
700	1	2	_aYamauchi, T.
700	1	2	_aYamauchi, T.
700	1	2	_aO'Keefe, D.D.
700	1	2	_aNúñez-Delicado, E.
700	1	2	_aGuillen, P.
700	1	2	_aCampistol, J.M.
700	1	2	_aWu, C.-J.
700	1	2	_aLu, L.-F.
700	1	2	_aEsteban, C.R.
700	1	2	_aIzpisua Belmonte, J.C.
856	4	0	_uhttps://drive.google.com/file/d/1XHJr6DfWyZ7Jly9U3ZTTCWP80qgHSqae/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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