Abstract

This Integrated Pre-Clinical/Clinical Program from City of Hope National Medical Center (COH) proposes to develop and improve methods for genetic treatment of HIV-1 using antiviral RNA. There are three basic science projects aimed at improved gene transfer, gene expression, and HIV inhibition using retroviral and lentiviral vectors. Project 1 at Children's Hospital Los Angeles will evaluate the expression of improved vectors in monocytes and T-cells after transduction of human hematopoietic stem cells. Project 2 at the Beckman Research Institute of COH (BRICOH) will study improved stability of expression of antiviral RNA target4ed to HIV. Project 3 at BRICOH is devoted to comparative studies of improved retroviral and lentiviral vectors. In Project 4, the Clinical Trials Center will complete two comparative trials of experimental autologous stem-cell transplantation (SCT) of CD34+ peripheral blood progenitor cells (PBPC) transduced with a retrovirus encoding a double hammerhead ribozyme targeted to TAT and REV. one study, in AIDS patients with non-Hodgkin's lymphoma, utilizes an ablative marrow conditioning regimen, and the other, in healthy HIV-1 infected persons, will use hydroxyurea for partial cytoreduction of marrow. The basic science and laboratory programs are supported by three core areas. The Administrative Center, will oversee the management of the basic science and clinical studies. The DNA/RNA Analytical Lab will evaluate marrow and blood specimens post transplantation for the presence and stability of expression of the ribozyme transgene. The Virology Lab, will provide support for HIV analyses and assessment of antiviral effects of new anti-HIV RNAs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
3P01AI046030-03S1
Application #
6401176
Study Section
Special Emphasis Panel (ZAI1-HSD-A (M1))
Program Officer
Cairns, Scott
Project Start
1999-09-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
3
Fiscal Year
2001
Total Cost
$317,960
Indirect Cost

  Institution

Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010

  Publications

Saetrom, Pål; Biesinger, Jacob; Li, Sierra M et al. (2009) A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Cancer Res 69:7459-65
Kowolik, Claudia M; Yam, Priscilla; Yu, Ying et al. (2003) HIV vector production mediated by Rev protein transduction. Mol Ther 8:324-31
Li, Ming-Jie; Bauer, Gerhard; Michienzi, Alessandro et al. (2003) Inhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs. Mol Ther 8:196-206
Paul, Cynthia P; Good, Paul D; Li, Shirley X L et al. (2003) Localized expression of small RNA inhibitors in human cells. Mol Ther 7:237-47
Michienzi, Alessandro; Li, Shirley; Zaia, John A et al. (2002) A nucleolar TAR decoy inhibitor of HIV-1 replication. Proc Natl Acad Sci U S A 99:14047-52
Chang, Zongli; Westaway, Shawn; Li, Shirley et al. (2002) Enhanced expression and HIV-1 inhibition of chimeric tRNA(Lys3)-ribozymes under dual U6 snRNA and tRNA promoters. Mol Ther 6:481-9
Strayer, David; Branco, Francisco; Zern, Mark A et al. (2002) Durability of transgene expression and vector integration: recombinant SV40-derived gene therapy vectors. Mol Ther 6:227-37
Lee, Nan Sook; Dohjima, Taikoh; Bauer, Gerhard et al. (2002) Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol 20:500-5
Yam, Priscilla Y; Li, Shulian; Wu, Jerry et al. (2002) Design of HIV vectors for efficient gene delivery into human hematopoietic cells. Mol Ther 5:479-84
Kowolik, C M; Hu, J; Yee, J K (2001) Locus control region of the human CD2 gene in a lentivirus vector confers position-independent transgene expression. J Virol 75:4641-8

Showing the most recent 10 out of 12 publications