Understanding the innate defences of T cells to lentiviruses

In this project we will characterise the role of interferon induced transmembrane (IFITM) proteins in inhibiting human T-cell transduction with viral vectors for gene therapy.

We will improve our cyclosporine-based IFITM inhibitors for use in T-cells by developing them into T-cell active PROteolysis TArgeted Chimeras (PROTACs). PROTACs recruit E3 ligase proteins to the target, driving potent inhibition by proteasomal degradation. PROTACs are also excellent tools to study the biology of IFITMs in T-cells.

This new knowledge and new reagents will take our understanding of the mechanisms of viral restriction in T-cells to the next level and facilitate improved therapeutic modification of T-cells for gene therapy.