Ribozyme-Mediated Breast Cancer Gene Therapy
Abstract
In our laboratory we have developed lentiviral vectors for use in anti-breast cancer gene therapy. Our specific goal for this project is to evaluate the feasibility of using lentiviral vectors that express anti-HER-2/neu antisense or ribozymes for the treatment of breast cancer. The advantage of lentiviral vectors over other vectors is that lentiviral vectors can transduce human cells with great efficiency. We have demonstrated that HIV-based lentiviral vectors can transduce a variety of human cell types with up to 99% efficiency, as measured by FACS analysis of GFP expression in vector-transduced cells. For example, Sup Tl cells can be routinely transduced with greater than 99% efficiency. This expression is stable with cells expressing high levels of GFP for greater than 60 days in culture. Primary human CD4+ T cells are routinely transduced with up to 95% efficiency. Strikingly, CD34+ hematopoietic stem cells are transduced with up to 90% efficiency in NOD/SCID mice, as assayed by measuring GFP expression in the SCID repopulating cell population (SRC). Finally, breast cancer cells can be efficiently transduced with a GFP expressing lentiviral vector. Constructs expressing an anti-HER-2/neu antisense/ribozyme payload have been constructed and are ready for testing in breast cancer cell lines in vitro and in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA391315
Entities
People
- Paula Marie Pitha-rowe
Organizations
- Johns Hopkins University