Abstract

This project will test the hypothesis that AAV vectors which are capable of transducing non-dividing cells and directing gene expression from independent transcriptional units can transduce anti-HIV genes into primitive self-renewing pluripotent hematopoietic stem cells in a stable fashion. Multivalent AAV vectors encoding various anti-HIV genes will be tested for their ability to confer resistance to HIV-1. Transduction efficiencies, vector integration and HIV-resistance will be evaluated in the differentiated progeny. The long term transcriptional status of AAV vector genomes will be evaluated to determine the fate of genes delivered by AAV vectors. This study is designed to provide information regarding the basic biology of gene transfer with AAV vectors in addition to the anti-viral efficacy, feasibility and safety of gene therapy of hematopoietic stem cells using multivalent AAV vectors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI040001-03
Application #
2672788
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1996-07-01
Project End
2000-05-31
Budget Start
1998-06-01
Budget End
2000-05-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

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

  Publications

Kissinger, Jessica C; Hermetz, Karen E; Woods, Keith M et al. (2018) Enrichment of Cryptosporidium parvum from in vitro culture as measured by total RNA and subsequent sequence analysis. Mol Biochem Parasitol 220:5-9
Hasan, Nur A; Grim, Christopher J; Lipp, Erin K et al. (2015) Deep-sea hydrothermal vent bacteria related to human pathogenic Vibrio species. Proc Natl Acad Sci U S A 112:E2813-9
Hasan, Nur A; Grim, Christopher J; Haley, Bradd J et al. (2010) Comparative genomics of clinical and environmental Vibrio mimicus. Proc Natl Acad Sci U S A 107:21134-9
Haley, Bradd J; Grim, Christopher J; Hasan, Nur A et al. (2010) Comparative genomic analysis reveals evidence of two novel Vibrio species closely related to V. cholerae. BMC Microbiol 10:154
Taviani, Elisa; Grim, Christopher J; Choi, Jinna et al. (2010) Discovery of novel Vibrio cholerae VSP-II genomic islands using comparative genomic analysis. FEMS Microbiol Lett 308:130-7
Chun, Jongsik; Grim, Christopher J; Hasan, Nur A et al. (2009) Comparative genomics reveals mechanism for short-term and long-term clonal transitions in pandemic Vibrio cholerae. Proc Natl Acad Sci U S A 106:15442-7
Santat, Leah; Paz, Helicia; Wong, Christie et al. (2005) Recombinant AAV2 transduction of primitive human hematopoietic stem cells capable of serial engraftment in immune-deficient mice. Proc Natl Acad Sci U S A 102:11053-8