Wild-type p53 gene transfer is not detrimental to normal cells in vivo: Implications for tumor gene therapy

Gianluca Bossi, Giuseppina Mazzaro, Alessandro Porrello, Marco Crescenzi, Silvia Soddu, Ada Sacchi

Research output: Contribution to journalArticle

Abstract

The p53 oncosuppressor is strictly maintained in an inactive form under normal conditions, while it is posttranslationally activated by a variety of stresses, enacting different protective biological functions. Since one critical issue in cancer gene therapy is tumor specificity, we asked whether the tight p53 regulation applies also to exogenously transferred p53. In principle, this type of regulation could allow p53 gene transfer in both normal and tumor cells to produce detrimental effects only in the latter ones. Here, we report that primary bone marrow cells infected with a p53 recombinant retrovirus and transplanted into irradiated mice reconstitute the hematopoietic system, with no detectable alterations in any of its compartments. Furthermore, simultaneous infection of leukemia and bone marrow cells depleted the neoplastic contamination, allowing lifelong, disease-free survival of 65% of the transplanted animals. These results show that exogenous p53 is controlled as tightly as the endogenous one, and opens the way to p53 gene therapy, without requiring tumor targeting.

Original languageEnglish
Pages (from-to)418-425
Number of pages8
JournalOncogene
Volume23
Issue number2
DOIs
Publication statusPublished - Jan 15 2004

Keywords

  • Gene therapy
  • Normal cells
  • p53
  • Retrovirus vector
  • Tumor targeting

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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