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CRISPR/Cas9 Genome Engineering in Engraftable Human Brain-Derived Neural Stem Cells.
Dever, Daniel P; Scharenberg, Samantha G; Camarena, Joab; Kildebeck, Eric J; Clark, Joseph T; Martin, Renata M; Bak, Rasmus O; Tang, Yuming; Dohse, Monika; Birgmeier, Johannes A; Jagadeesh, Karthik A; Bejerano, Gill; Tsukamoto, Ann; Gomez-Ospina, Natalia; Uchida, Nobuko; Porteus, Matthew H.
Afiliação
  • Dever DP; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Scharenberg SG; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Camarena J; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Kildebeck EJ; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Clark JT; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Martin RM; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Bak RO; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Tang Y; StemCells Inc, Newark, CA 94560, USA.
  • Dohse M; StemCells Inc, Newark, CA 94560, USA.
  • Birgmeier JA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
  • Jagadeesh KA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
  • Bejerano G; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
  • Tsukamoto A; ReGen Med Division, BOCO Silicon Valley, Palo Alto, CA 94303, USA.
  • Gomez-Ospina N; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Uchida N; ReGen Med Division, BOCO Silicon Valley, Palo Alto, CA 94303, USA. Electronic address: nobuko.uchida@bocosiliconvalley.com.
  • Porteus MH; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA. Electronic address: mporteus@stanford.edu.
iScience ; 15: 524-535, 2019 May 31.
Article em En | MEDLINE | ID: mdl-31132746
ABSTRACT
Human neural stem cells (NSCs) offer therapeutic potential for neurodegenerative diseases, such as inherited monogenic nervous system disorders, and neural injuries. Gene editing in NSCs (GE-NSCs) could enhance their therapeutic potential. We show that NSCs are amenable to gene targeting at multiple loci using Cas9 mRNA with synthetic chemically modified guide RNAs along with DNA donor templates. Transplantation of GE-NSC into oligodendrocyte mutant shiverer-immunodeficient mice showed that GE-NSCs migrate and differentiate into astrocytes, neurons, and myelin-producing oligodendrocytes, highlighting the fact that GE-NSCs retain their NSC characteristics of self-renewal and site-specific global migration and differentiation. To show the therapeutic potential of GE-NSCs, we generated GALC lysosomal enzyme overexpressing GE-NSCs that are able to cross-correct GALC enzyme activity through the mannose-6-phosphate receptor pathway. These GE-NSCs have the potential to be an investigational cell and gene therapy for a range of neurodegenerative disorders and injuries of the central nervous system, including lysosomal storage disorders.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: IScience Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos