This application concentrates upon determining the rates and spectra of mutation arising during a single cycle of HIV and MLV vector viral replication.One objective is to develop HIV-based packaging cells needed to carry out HIV mutation rate studies. Once such HIV-based packaging cells are available, they will be utilized for HIV forward mutation rate (loss-of- function) analysis. One of the genes to be employed as a reporter is the lacZa gene. The studies to be done with MLV are an extension of already described work indicating that MLV vectors can undergo genetic rearrangement at a particularly high rate, including a high rate of transduction of sequences from infected cells. Experiments are proposed to extend MLV mutation rate analysis to a number of genes to address the sequence-dependence of mutational events.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA050777-14
Application #
6626590
Study Section
Special Emphasis Panel (ZRG5-AARR-1 (01))
Program Officer
Cole, John S
Project Start
1989-06-15
Project End
2004-12-31
Budget Start
2003-01-01
Budget End
2004-12-31
Support Year
14
Fiscal Year
2003
Total Cost
$273,724
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Genetics
Type
Schools of Medicine
DUNS #
617022384
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Chen, Chiann-Chyi; Rivera, Amariliz; Dougherty, Joseph P et al. (2004) Complete protection from relapsing experimental autoimmune encephalomyelitis induced by syngeneic B cells expressing the autoantigen. Blood 103:4616-8
Oertel, Michael; Rosencrantz, Richard; Chen, Yuan-Qing et al. (2003) Repopulation of rat liver by fetal hepatoblasts and adult hepatocytes transduced ex vivo with lentiviral vectors. Hepatology 37:994-1005
Rivera, Amariliz; Chen, Chiann-Chyi; Dougherty, Joseph P et al. (2003) Host stem cells can selectively reconstitute missing lymphoid lineages in irradiation bone marrow chimeras. Blood 101:4347-54
Rivera, A; Chen, C C; Ron, N et al. (2001) Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations. Int Immunol 13:1583-93
Chen, C; Rivera, A; Ron, N et al. (2001) A gene therapy approach for treating T-cell-mediated autoimmune diseases. Blood 97:886-94
Preston, B D; Dougherty, J P (1996) Mechanisms of retroviral mutation. Trends Microbiol 4:16-21
Parthasarathi, S; Varela-Echavarria, A; Ron, Y et al. (1995) Genetic rearrangements occurring during a single cycle of murine leukemia virus vector replication: characterization and implications. J Virol 69:7991-8000