G2 Cell Cycle Arrest and Cyclophilin A in Lentiviral Gene Transfer

Shangming Zhang, Guiandre Joseph, Karen Pollok, Lionel Berthoux, Lakshmi Sastry, Jeremy Luban, Kenneth Cornetta

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Lentiviral vectors derived from the human immunodeficiency virus-1 (HIV-1) have a higher propensity to transduce nondividing cells compared to vectors based on oncoretroviruses. We report here that genistein, a previously known protein tyrosine kinase (PTK) inhibitor and G2 cell cycle arrest inducer, significantly enhanced lentiviral transduction in a dose-dependent manner. Increased transduction, as measured by vector expression, was seen in a variety of human cell lines, murine primary lymphocytes, and primary human CD34+ peripheral blood progenitor cells as well. Increased vector expression was also associated with an increase in vector DNA copy number, as assessed by quantitative PCR. Genistein-mediated G2 cell cycle arrest, rather than PTK inhibition, appears to be the major factor responsible for increased gene transfer. Genistein also increases cyclophilin A (CypA) protein, a cellular protein important for efficient HIV-1 infection. While we show that CypA-/- Jurkat cells transduce poorly with lentiviral vectors, genistein does increase gene transfer in CypA-deficient cells. CypA and G2 cell cycle arrest appear to be two independent factors important for efficient lentiviral gene transfer. The role of genistein and other G2-arresting agents may be useful for improving the efficiency of lentiviral gene therapy.

Original languageEnglish (US)
Pages (from-to)546-554
Number of pages9
JournalMolecular Therapy
Volume14
Issue number4
DOIs
StatePublished - Oct 1 2006

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Keywords

  • cyclophilin A
  • cyclosporin A
  • gene therapy
  • genistein
  • human immunodeficiency virus-1
  • lentiviral vector
  • vesicular stomatitis virus glycoprotein

ASJC Scopus subject areas

  • Molecular Biology

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