• The efficacy of the lentiviral vector system: Production systems, vector titer, vector specific activity, duration of transgene expression.
• The safety of the retro/lentiviral vector system: Vector mobilization, insertional mutagenesis, contamination with endogenous retroviruses.
• Basic HIV biology: The role of episomal HIV in the viral lifecycle, variations of RT products, HIV silencing, packaging signal mapping.

Current translational challenges/questions which keeps gene therapy within the bounds of fatal diseases:

• Patient to patient variations in the outcomes of clinical trials
• Discrepancies between the outcomes of preclinical animal models and clinical trials

Working Hypothesis

The current preclinical studies (premised on a single mouse strain) ignore the host factors effects on:

• The efficacy and safety of viral vector gene delivery
• The ability of a particular mouse strain to accurately emulate specific gene delivery traits in humans

New Directions

• Treating the outcomes of gene therapy as a HIGHLY multigenic/ complex trait/phenotype
• Moving from animal models based on single mouse strain concept
• Can we target the modifier genes?

Model System of Interest

We employ the collaborative cross mouse panel to identify host factors affecting lentiviral vector transduction and HIV biology

Relevant Publications

Suwanmanee and Kafri et al. (2017) http://dx.doi.org/10.1016/j.omtm.2017.03.009.
Hu and Kafri et al. (2025). https://doi.org/10.3390/v17020276