Overview

Our expertise is using HIV-1-based vectors for gene delivery. HIV-1 vectors can integrate and express genes in both dividing and non-dividing cells and can efficiently transfer complex genetic structures. HIV-1 vectors are also appropriate for introducing persistent silencing, generating transgenic animals, investigation of lentiviral life cycle, along with straightforward transgene delivery to target cells. However, for clinical application of the vectors, we need to solve two major problems; relatively low transduction efficiency of primary cells and the concern regarding the safety of the vectors.

In order to improve the vector transduction efficiency, we are studying cellular factors which affect HIV-1 production/infection. We are particularly interested in innate/intrinsic antiviral activities in primary cells. We hope that better understanding of potent antiviral factors, including TRIM5alpha, will give us a clue to develop a better HIV-1 vector system and a novel therapeutic approach for HIV-1 infection. In order to minimize the safety concern, we are also establishing a high titer packaging cell line for clinical grade HIV-1 vector production.

Our projects include i) Characterization of the TRIM5alpha-mediated block of HIV-1 production, ii) Modification of HIV-1 vectors for primary cell transduction, iii) Establishment of clinical grade packaging cell lines for HIV-1 vectors, iv) Self-regulating HIV-1 vectors for Hemophilia gene therapy, v) Use of intrinsic restriction factors for HIV-1 gene therapy, and vi) Characterization of oncolytic properties of vesicular stomatitis virus.