The AIDS lab, under the direction of Dr. S. Li, will perform all confirmatory antiviral analyses for the scientific Projects 1 and 2 involving anti-HIV inhibitory activity of new antiviral RNAi designs. In addition, the Core will provide the initial assessment of in vitro antiviral effects of the SHIV vector to be tested in the macaque model in Project 3. The Core will provide HIV isolation and analysis for the clinical trial that will monitor HIV isolation and assessment of HIV sequences during the phase 1 trial. Finally, this Core will be responsible for the release testing for all lots of new lentivirus vectors prepared in Project 2 prior to use in the other laboratory projects and of the RCL testing in the clinical trial.
The specific aims are:
Specific Aim 1 : To assist Projects 1-3 in evaluation of new anti-HIV constructs for potential anti-HIV effect in vitro by performing transient co-transfection assays and post transduction HIV or SHIV infectivity challenges. Thelaboratory will perform RT, p24 or p27, and post challenge PBMC survival assays as confirmation of the new vector development experimentation.
Specific Aim 2 : To assist the clinical trial in Project 4 by performing all HIV-1 isolation required by the study and tocoordinate the processing of all clinical specimens. HIV-1 isolates will be evaluated for resistance to RNAi by monitoring sequence variation within the RNAi targeted region of rev.
Specific Aim 3 : To perform the release tests for replication competent lentivirus on laboratory grade vectors produced in Projects 1 and 2, and to evaluate HIV-1 isolates from pHIV7-shlI vector-treated research subjects for the presence of recombination with the pHIV7-shII sequences.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI061839-04
Application #
7480231
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
4
Fiscal Year
2007
Total Cost
$140,636
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
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Zheng, Weiyan; Wang, Yingjia; Chang, Tammy et al. (2013) Significant differences in genotoxicity induced by retrovirus integration in human T cells and induced pluripotent stem cells. Gene 519:142-9
Trobridge, Grant D; Horn, Peter A; Beard, Brian C et al. (2012) Large animal models for foamy virus vector gene therapy. Viruses 4:3572-88
Kiem, Hans-Peter; Ironside, Christina; Beard, Brian C et al. (2010) A retroviral vector common integration site between leupaxin and zinc finger protein 91 (ZFP91) observed in baboon hematopoietic repopulating cells. Exp Hematol 38:819-22, 822.e1-3
Trobridge, Grant D; Wu, Robert A; Hansen, Michael et al. (2010) Cocal-pseudotyped lentiviral vectors resist inactivation by human serum and efficiently transduce primate hematopoietic repopulating cells. Mol Ther 18:725-33
DiGiusto, David L; Krishnan, Amrita; Li, Lijing et al. (2010) RNA-based gene therapy for HIV with lentiviral vector-modified CD34(+) cells in patients undergoing transplantation for AIDS-related lymphoma. Sci Transl Med 2:36ra43
Beard, Brian C; Trobridge, Grant D; Ironside, Christina et al. (2010) Efficient and stable MGMT-mediated selection of long-term repopulating stem cells in nonhuman primates. J Clin Invest 120:2345-54
Trobridge, G D; Kiem, H-P (2010) Large animal models of hematopoietic stem cell gene therapy. Gene Ther 17:939-48
Kiem, H-P; Wu, R A; Sun, G et al. (2010) Foamy combinatorial anti-HIV vectors with MGMTP140K potently inhibit HIV-1 and SHIV replication and mediate selection in vivo. Gene Ther 17:37-49
Bonig, Halvard; Watts, Korashon L; Chang, Kai-Hsin et al. (2009) Concurrent blockade of alpha4-integrin and CXCR4 in hematopoietic stem/progenitor cell mobilization. Stem Cells 27:836-7

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