The ability of HIV-1 and other lentiviruses to transduce non-dividing cells prompt the development of an HIV-1 based gene delivery system. The novel lentivirus vectors proved efficient at transducing various tissues in vivo (brain, liver, muscle, retina, and hematopoietic stem cells) without any detectable pathology. However we believe that further improvements in: vector production, transgene expression and regulation, and better characterization of the mechanism responsible for the development of immune response against vector delivered transgenes are required before we can consider the use of the lentiviral system in clinical trials.
Vector production: To improve vector production our laboratory is focused on the development of an inducible lentivirus vector packaging cell line which is a prerequisite for human clinical trials. Packaging cell lines facilitate large vector production and provide new safety measurements, which are required for clinical trials.
Transgene expression: To improve transgene expression we use MLV/HIV-1 chimera vectors to identify and to remove cis sequences that down-regulate transgene expression from HIV-1 vectors.
Regulation of transgene expression: To allow regulation of transgene expression in vivo we develop tetracycline inducible lentivirus vectors. Our objectives are to reduce non-regulated basal transgene production and to minimize the risk of developing immune response against vector transduced cells.
Animal models: Using hemophilic mice and canines enables us to test the efficacy and safety of our newly developed lentivirus vectors.
HIV-1 Biology
Non-integrated
HIV-1 particles: Our laboratory is focused
on characterizing the mechanism involved in down-regulation
of gene expression from non-integrated HIV-1 genome.
Virus host interaction: We are currently characterizing
the effects of unique point mutations in the HIV-1
gag and pol genes on the efficiency of vector particles
at transducing a variety of primary cells.
