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

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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
Publication statusPublished - Oct 1 2006

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Zhang, S., Joseph, G., Pollok, K., Berthoux, L., Sastry, L., Luban, J., & Cornetta, K. (2006). G2 Cell Cycle Arrest and Cyclophilin A in Lentiviral Gene Transfer. Molecular Therapy, 14(4), 546-554. https://doi.org/10.1016/j.ymthe.2006.05.022