Application of HSVtk suicide gene to X-SCID gene therapy: Ganciclovir treatment offsets gene corrected X-SCID B cells

Toru Uchiyama, Satoru Kumaki, Yoshinori Ishikawa, Masafumi Onodera, Miki Sato, Wei Du, Yoji Sasahara, Nobuyuki Tanaka, Kazuo Sugamura, Shigeru Tsuchiya

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Recently, a serious adverse effect of uncontrolled clonal T cell proliferation due to insertional mutagenesis of retroviral vector was reported in X-SCID gene therapy clinical trial. To offset the side effect, we have incorporated a suicide gene into therapeutic retroviral vector for selective elimination of transduced cells. In this study, B-cell lines from two X-SCID patients were transduced with bicistronic retroviral vector carrying human γc chain cDNA and Herpes simplex virus thymidine kinase gene. After confirmation of functional reconstitution of the γc chain, the cells were treated with ganciclovir (GCV). The γc chain positive cells were eliminated under low concentration without cytotoxicity on untransduced cells and have not reappeared at least for 5 months. Furthermore, the γc chain transduced cells were still sensitive to GCV after five months. These results demonstrated the efficacy of the suicide gene therapy although further in vivo studies are required to assess feasibility of this approach in clinical trial.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalBiochemical and biophysical research communications
Volume341
Issue number2
DOIs
Publication statusPublished - 2006 Mar 10

Keywords

  • Gene therapy
  • HSVtk
  • Retroviral vector
  • Suicide gene
  • X-SCID
  • γc chain

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Application of HSVtk suicide gene to X-SCID gene therapy: Ganciclovir treatment offsets gene corrected X-SCID B cells'. Together they form a unique fingerprint.

Cite this