Powell, Jackson E.;
Lim, Colin K. W.;
Krishnan, Ramya;
McCallister, Tristan X.;
Saporito-Magriña, Christian;
Zeballos, Maria A.;
McPheron, Garrett D.;
Gaj, Thomas
Targeted gene silencing in the nervous system with CRISPR-Cas13
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Medientyp:
E-Artikel
Titel:
Targeted gene silencing in the nervous system with CRISPR-Cas13
Beteiligte:
Powell, Jackson E.;
Lim, Colin K. W.;
Krishnan, Ramya;
McCallister, Tristan X.;
Saporito-Magriña, Christian;
Zeballos, Maria A.;
McPheron, Garrett D.;
Gaj, Thomas
Erschienen:
American Association for the Advancement of Science (AAAS), 2022
Erschienen in:
Science Advances, 8 (2022) 3
Sprache:
Englisch
DOI:
10.1126/sciadv.abk2485
ISSN:
2375-2548
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>Cas13 nucleases are a class of programmable RNA-targeting CRISPR effector proteins that are capable of silencing target gene expression in mammalian cells. Here, we demonstrate that RfxCas13d, a Cas13 ortholog with favorable characteristics to other family members, can be delivered to the mouse spinal cord and brain to silence neurodegeneration-associated genes. Intrathecally delivering an adeno-associated virus vector encoding an RfxCas13d variant programmed to target superoxide dismutase 1 (SOD1), a protein whose mutation can cause amyotrophic lateral sclerosis, reduced SOD1 mRNA and protein in the spinal cord by >50% and improved outcomes in a mouse model of the disorder. We further show that intrastriatally delivering an RfxCas13d variant programmed to target huntingtin (HTT), a protein whose mutation is causative for Huntington’s disease, led to a ~50% reduction in HTT protein in the mouse brain. Our results establish RfxCas13d as a versatile platform for knocking down gene expression in the nervous system.</jats:p>