MiniCAFE, a CRISPR/Cas9-based compact and potent transcriptional activator, elicits gene expression in vivo.
Nucleic Acids Res
; 49(7): 4171-4185, 2021 04 19.
Article
em En
| MEDLINE
| ID: mdl-33751124
ABSTRACT
CRISPR-mediated gene activation (CRISPRa) is a promising therapeutic gene editing strategy without inducing DNA double-strand breaks (DSBs). However, in vivo implementation of these CRISPRa systems remains a challenge. Here, we report a compact and robust miniCas9 activator (termed miniCAFE) for in vivo activation of endogenous target genes. The system relies on recruitment of an engineered minimal nuclease-null Cas9 from Campylobacter jejuni and potent transcriptional activators to a target locus by a single guide RNA. It enables robust gene activation in human cells even with a single DNA copy and is able to promote lifespan of Caenorhabditis elegans through activation of longevity-regulating genes. As proof-of-concept, delivered within an all-in-one adeno-associated virus (AAV), miniCAFE can activate Fgf21 expression in the liver and regulate energy metabolism in adult mice. Thus, miniCAFE holds great therapeutic potential against human diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Guia de Cinetoplastídeos
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Fatores de Crescimento de Fibroblastos
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Sistemas CRISPR-Cas
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Edição de Genes
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Proteína 9 Associada à CRISPR
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article