A Single H1 Promoter Can Drive Both Guide RNA and Endonuclease Expression in the CRISPR-Cas9 System

The RNA-guided endonuclease Cas9 (CRISPR-Cas9) genome editing system has been widely used for biomedical research and holds great potential for therapeutic applications in eukaryotes. The conventional vector-based CRISPR-Cas9 delivery system requires two different RNA polymerase promoters for expres...

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Detalles Bibliográficos
Autores: Gao, Zongliang, Herrera, Elena, Berkhout, Ben
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/415230
Acceso en línea:http://hdl.handle.net/10261/415230
https://api.elsevier.com/content/abstract/scopus_id/85057736079
Access Level:acceso abierto
Palabra clave:CRISPR-Cas9
Cas9 protein expression
H1 promoter
RNA polymerase III and II
Dual RNA polymerase promoter
Guide RNA expression
Lentiviral vector
Viral delivery
Descripción
Sumario:The RNA-guided endonuclease Cas9 (CRISPR-Cas9) genome editing system has been widely used for biomedical research and holds great potential for therapeutic applications in eukaryotes. The conventional vector-based CRISPR-Cas9 delivery system requires two different RNA polymerase promoters for expression of the guide RNA (gRNA) and Cas9 endonuclease. The large size and relative complexity of such CRISPR transgene cassettes impede their broad implementation, especially in gene therapy applications with viral vectors that have a limited packaging capacity. Here, we report the design of a single-promoter-driven CRISPR-Cas9 system that uses the dual-polymerase (Pol II and Pol III) activity of the H1 promoter. This size reduction strategy of the vector insert provides a significant titer advantage in the lentiviral vector over the regular CRISPR system.