In vivo stable transduction of humanized liver tissue in chimeric mice via high-capacity adenovirus-lentivirus hybrid vector

Shuji Kubo, Miho Kataoka, Chise Tateno, Katsutoshi Yoshizato, Yoshiko Kawasaki, Takahiro Kimura, Emmanuelle Faure-Kumar, Donna J. Palmer, Philip Ng, Haruki Okamura, Noriyuki Kasahara

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

We developed hybrid vectors employing high-capacity adenovirus as a first-stage carrier encoding all the components required for in situ production of a second-stage lentivirus, thereby achieving stable transgene expression in secondary target cells. Such vectors have never previously been tested in normal tissues, because of the scarcity of suitable in vivo systems permissive for second-stage lentivirus assembly. Here we employed a novel murine model in which endogenous liver tissue is extensively reconstituted with engrafted human hepatocytes, and successfully achieved stable transduction by the second-stage lentivirus produced in situ from first-stage adenovirus. This represents the first demonstration of the functionality of adenoviral-lentiviral hybrid vectors in a normal parenchymal organ in vivo.

Original languageEnglish (US)
Pages (from-to)40-50
Number of pages11
JournalHuman gene therapy
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Kubo, S., Kataoka, M., Tateno, C., Yoshizato, K., Kawasaki, Y., Kimura, T., Faure-Kumar, E., Palmer, D. J., Ng, P., Okamura, H., & Kasahara, N. (2010). In vivo stable transduction of humanized liver tissue in chimeric mice via high-capacity adenovirus-lentivirus hybrid vector. Human gene therapy, 21(1), 40-50. https://doi.org/10.1089/hum.2009.027