Improving Retroviral Vectors for Gene Therapy of Prostate Cancer

Abstract

This project aims to increase the transduction efficiency and target cell-specificity of retroviral vectors, thereby improving gene transfer to prostate cancer cells. We have developed a novel replication-competent retroviral (RCR) vector system for gene transfer to solid tumors which is highly efficient, as each tumor cell which is successfully transduced becomes itself a virus-producing cell and initiates further infection events even after the initial injection. Through this project, we have tested a number of strategies for targeting these replicating vectors specifically and exclusively to tumor cells in order to limit and control the replicative process and minimize the risk to normal cells. We have engineered the prostate-specific probasin promoter into the retroviral long terminal repeat (LTR), and used this construct to establish producer cell lines derived from prostate cancer cells that express androgen receptors. We have optimized the design of the probasin/LTR hybrid promoter construct, and we have demonstrated the prostate-specificity of probasin-targeted RCR vector - replication and suicide gene transfer in culture and in vivo.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2003
Accession Number
ADA419147

Entities

People

  • Noriyuki Kasahara

Organizations

  • University of Southern California

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Epithelial Cells
  • Gene Expression
  • Gene Therapy
  • Medical Personnel
  • Neoplasms
  • Nucleosides
  • Prostate Cancer
  • Proteins
  • Therapy
  • Tissues

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech