CRISPR/Cas9 directed to the Ube3a antisense transcript improves Angelman syndrome phenotype in mice.
Gene editing holds the potential to correct mutations and cure devastating genetic disorders. The technology has not yet proven efficacious for therapeutic use in CNS diseases with ubiquitous neuronal defects. Angelman syndrome (AS), a severe neurodevelopmental disorder, is caused by a lack of mater...
| Publicado en: | Journal of Clinical Investigation Vol. 131; no. 5; pp. 1 - 8 |
|---|---|
| Autores principales: | , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
American Society for Clinical Investigation
Mar2021
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=149458376&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 149458376 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00219738 0YX jtl: Journal of Clinical Investigation issn: 00219738 maglogo: N pubinfo: dt: Mar2021 vid: 131 iid: 5 pid: 11983 pub: American Society for Clinical Investigation place: Ann Arbor, Michigan artinfo: ui: 149458376 149458376 NLM33411694 149458376 10.1172/JCI142574 NLM33411694 149458376 ppf: 1 ppct: 7 formats: tig: atl: CRISPR/Cas9 directed to the Ube3a antisense transcript improves Angelman syndrome phenotype in mice. aug: au: Schmid, Ralf S. Xuefeng Deng Panikker, Priyalakshmi Msackyi, Msema Breton, Camilo Wilson, James M. Deng, Xuefeng affil: Gene Therapy Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA sug: subj: RNA Metabolism Gene Expression Brain Metabolism Enzymes Metabolism Angelman Syndrome Metabolism Angelman Syndrome Therapy RNA Animal Studies Enzymes Mice Human Angelman Syndrome Comparative Studies Multicenter Studies Evaluation Research Validation Studies ab: Gene editing holds the potential to correct mutations and cure devastating genetic disorders. The technology has not yet proven efficacious for therapeutic use in CNS diseases with ubiquitous neuronal defects. Angelman syndrome (AS), a severe neurodevelopmental disorder, is caused by a lack of maternal expression of the UBE3A gene. Because of genomic imprinting, only neurons are affected. One therapeutic approach focuses on the intact paternal UBE3A copy in patients with AS that is silenced by an antisense transcript (UBE3A-ATS). We show here that gene editing of Ube3a-ATS in the mouse brain resulted in the formation of base pair insertions/deletions (indels) in neurons and the subsequent unsilencing of the paternal Ube3a allele in neurons, which partially corrected the behavioral phenotype of a murine AS model. This study provides compelling evidence to further investigate editing of the homologous region of the human UBE3A-ATS because this may provide a lasting therapeutic effect for patients with AS. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|