Kafri Lab

Laboratory phone: 919.843.7103

Our lab is focused on the development of HIV-1 vectors for gene therapy of genetic and acquired human diseases, including hemophilia, Krabbe disease, and prostate cancer. In addition, we are employing various retroviral vector systems to study HIV-1 biology.

Gene Therapy

The ability of HIV-1 and other lentiviruses to transduce non-dividing cells prompted 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 mechanisms 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. Packaging cell lines facilitate large vector production and provide additional safety measurements, and are a prerequisite for human clinical trials.

Regulation of transgene expression: To allow regulation of transgene expression in-vivo, we are developing various inducible lentivirus vector systems. Our objectives are to reduce non-regulated basal transgene production and to minimize the risk of developing immune response against vector transduced cells.

Vector biosafety: To minimize the risks of insertional mutagenesis, we are developing integration-defective lentiviral vectors. Our goals are to overcome the epigenetic silencing of episomal vector genomes, and to minimize the rates of illegitimate integrase-independent integration of vector genomes.

Animal models: Using hemophilic mice and canines enables us to test the efficacy and safety of our newly developed lentivirus vectors.

HIV-1 Biology

The role of episomal HIV-1 in the viral life cycle: Our laboratory is focused on characterizing the molecular mechanisms that down-regulate gene expression from non-integrated HIV-1 genomes.  In addition, we study the interactions between integrated and episomal viral genomes as well as the effects of gut bacteria on the episomal and integrated viral genomes.

HIV-1 latency: We are currently investigating the epigenetic mechanisms involved in transcriptional silencing of integrated HIV-1. Specifically, we are interested in the host factors involved in epigenetic silencing of integrated HIV-1 genomes, the cis elements in the HIV-1 genome (which serve as target sites for transcriptional silencing), and the effects of the site of viral integration on gene expression.