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Adenine base editing in an adult mouse model of tyrosinaemia.
Song, Chun-Qing; Jiang, Tingting; Richter, Michelle; Rhym, Luke H; Koblan, Luke W; Zafra, Maria Paz; Schatoff, Emma M; Doman, Jordan L; Cao, Yueying; Dow, Lukas E; Zhu, Lihua Julie; Anderson, Daniel G; Liu, David R; Yin, Hao; Xue, Wen.
Afiliação
  • Song CQ; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
  • Jiang T; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
  • Richter M; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
  • Rhym LH; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.
  • Koblan LW; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zafra MP; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Schatoff EM; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Doman JL; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
  • Cao Y; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.
  • Dow LE; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zhu LJ; Sandra and Edward Meyer Cancer Center, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  • Anderson DG; Sandra and Edward Meyer Cancer Center, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  • Liu DR; Weill Cornell/Rockefeller/Sloan Kettering Tri-I MD-PhD program, New York, NY, USA.
  • Yin H; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
  • Xue W; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.
Nat Biomed Eng ; 4(1): 125-130, 2020 01.
Article em En | MEDLINE | ID: mdl-31740768
ABSTRACT
In contrast to traditional CRISPR-Cas9 homology-directed repair, base editing can correct point mutations without supplying a DNA-repair template. Here we show in a mouse model of tyrosinaemia that hydrodynamic tail-vein injection of plasmid DNA encoding the adenine base editor (ABE) and a single-guide RNA (sgRNA) can correct an A>G splice-site mutation. ABE treatment partially restored splicing, generated fumarylacetoacetate hydrolase (FAH)-positive hepatocytes in the liver, and rescued weight loss in mice. We also generated FAH+ hepatocytes in the liver via lipid-nanoparticle-mediated delivery of a chemically modified sgRNA and an mRNA of a codon-optimized base editor that displayed higher base-editing efficiency than the standard ABEs. Our findings suggest that adenine base editing can be used for the correction of genetic diseases in adult animals.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenina / Tirosinemias / Edição de Genes Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Nat Biomed Eng Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenina / Tirosinemias / Edição de Genes Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Nat Biomed Eng Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos