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Selection of an Efficient AAV Vector for Robust CNS Transgene Expression.
Hanlon, Killian S; Meltzer, Jonah C; Buzhdygan, Tetyana; Cheng, Ming J; Sena-Esteves, Miguel; Bennett, Rachel E; Sullivan, Timothy P; Razmpour, Roshanak; Gong, Yi; Ng, Carrie; Nammour, Josette; Maiz, Daniela; Dujardin, Simon; Ramirez, Servio H; Hudry, Eloise; Maguire, Casey A.
Afiliação
  • Hanlon KS; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Meltzer JC; Molecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129.
  • Buzhdygan T; Harvard Medical School, Boston, MA 02115, USA.
  • Cheng MJ; Harvard Medical School, Boston, MA 02115, USA.
  • Sena-Esteves M; Alzheimer's Disease Research Laboratory, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
  • Bennett RE; Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
  • Sullivan TP; Shriners Hospital's Pediatric Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
  • Razmpour R; Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
  • Gong Y; Molecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129.
  • Ng C; Harvard Medical School, Boston, MA 02115, USA.
  • Nammour J; University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Maiz D; Harvard Medical School, Boston, MA 02115, USA.
  • Dujardin S; Alzheimer's Disease Research Laboratory, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
  • Ramirez SH; Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
  • Hudry E; Shriners Hospital's Pediatric Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
  • Maguire CA; Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Mol Ther Methods Clin Dev ; 15: 320-332, 2019 Dec 13.
Article em En | MEDLINE | ID: mdl-31788496
Adeno-associated virus (AAV) capsid libraries have generated improved transgene delivery vectors. We designed an AAV library construct, iTransduce, that combines a peptide library on the AAV9 capsid with a Cre cassette to enable sensitive detection of transgene expression. After only two selection rounds of the library delivered intravenously in transgenic mice carrying a Cre-inducible fluorescent protein, we flow sorted fluorescent cells from brain, and DNA sequencing revealed two dominant capsids. One of the capsids, termed AAV-F, mediated transgene expression in the brain cortex more than 65-fold (astrocytes) and 171-fold (neurons) higher than the parental AAV9. High transduction efficiency was sex-independent and sustained in two mouse strains (C57BL/6 and BALB/c), making it a highly useful capsid for CNS transduction of mice. Future work in large animal models will test the translation potential of AAV-F.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2019 Tipo de documento: Article