Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain

Details

• Alternative Title:
  Nat Biotechnol
• Personal Author:
  Deverman, Benjamin E. ; Pravdo, Piers L. ; Simpson, Bryan P. ; Kumar, Sripriya Ravindra ; Chan, Ken Y. ; Banerjee, Abhik ; Wu, Wei-Li ; Yang, Bin ; Huber, Nina ; Pasca, Sergiu P. ; Gradinaru, Viviana
• Description:
  Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination-based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations in vivo. We use CREATE to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection. One variant, AAV-PHP.B, transfers genes throughout the CNS with an efficiency that is at least 40-fold greater than that of the current standard, AAV9 (refs. 14,15,16,17), and transduces the majority of astrocytes and neurons across multiple CNS regions. In vitro, it transduces human neurons and astrocytes more efficiently than does AAV9, demonstrating the potential of CREATE to produce customized AAV vectors for biomedical applications.
• Subjects:
  Animals Article Dependovirus Female Genetic Engineering Genetic Vectors HEK293 Cells Humans Integrases Mice Transfection

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• Source:
  Nat Biotechnol. 34(2):204-209
• Pubmed ID:
  26829320
• Pubmed Central ID:
  PMC5088052
• Document Type:
  Journal Article
• Funding:
  1R21MH103824-01/MH/NIMH NIH HHSUnited States/ ; DP2 NS087949/NS/NINDS NIH HHSUnited States/ ; 1DP2NS087949/DP/NCCDPHP CDC HHSUnited States/ ; R21 MH103824/MH/NIMH NIH HHSUnited States/ ; 1R01MH100900/MH/NIMH NIH HHSUnited States/ ; R01MH107800/MH/NIMH NIH HHSUnited States/ ; R01 MH107800/MH/NIMH NIH HHSUnited States/ ; U01 NS090577/NS/NINDS NIH HHSUnited States/ ; R01 AG047664/AG/NIA NIH HHSUnited States/ ; R01 MH100900/MH/NIMH NIH HHSUnited States/ ; 1R01AG047664/AG/NIA NIH HHSUnited States/ ; 1U01NS090577/NS/NINDS NIH HHSUnited States/ ; 1R01MH100900-02S1/MH/NIMH NIH HHSUnited States/
• Volume:
  34
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:f8c779826761317f5300f2a46f8737c2ab486069b913198286610534e001b0a4
• Download URL:
  https://stacks.cdc.gov/view/cdc/42705/cdc_42705_DS1.pdf
• File Type:
  [PDF - 2.06 MB ]