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Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives.
Xu, Xiang-Ru Shannon; Bulger, Emily A; Gantz, Valentino M; Klanseck, Carissa; Heimler, Stephanie R; Auradkar, Ankush; Bennett, Jared B; Miller, Lauren Ashley; Leahy, Sarah; Juste, Sara Sanz; Buchman, Anna; Akbari, Omar S; Marshall, John M; Bier, Ethan.
Afiliación
  • Xu XS; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA.
  • Bulger EA; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, and Glads
  • Gantz VM; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA.
  • Klanseck C; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA.
  • Heimler SR; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA.
  • Auradkar A; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA.
  • Bennett JB; Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Miller LA; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA.
  • Leahy S; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA.
  • Juste SS; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA.
  • Buchman A; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA.
  • Akbari OS; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA.
  • Marshall JM; Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, CA, USA; Innovative Genomics Institute, Berkeley, CA, USA.
  • Bier E; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA. Electronic address: ebier@ucsd.edu.
Mol Cell ; 80(2): 246-262.e4, 2020 10 15.
Article en En | MEDLINE | ID: mdl-32949493
ABSTRACT
CRISPR-Cas9-based gene drive systems possess the inherent capacity to spread progressively throughout target populations. Here we describe two self-copying (or active) guide RNA-only genetic elements, called e-CHACRs and ERACRs. These elements use Cas9 produced in trans by a gene drive either to inactivate the cas9 transgene (e-CHACRs) or to delete and replace the gene drive (ERACRs). e-CHACRs can be inserted at various genomic locations and carry two or more gRNAs, the first copying the e-CHACR and the second mutating and inactivating the cas9 transgene. Alternatively, ERACRs are inserted at the same genomic location as a gene drive, carrying two gRNAs that cut on either side of the gene drive to excise it. e-CHACRs efficiently inactivate Cas9 and can drive to completion in cage experiments. Similarly, ERACRs, particularly those carrying a recoded cDNA-restoring endogenous gene activity, can drive reliably to fully replace a gene drive. We compare the strengths of these two systems.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Eliminación de Gen / Tecnología de Genética Dirigida Límite: Animals Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
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PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Eliminación de Gen / Tecnología de Genética Dirigida Límite: Animals Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos