[835] Protein and peptide engineering for medicine

With a focus on infectious diseases and immuno-oncology, we engineer proteins and peptides to identify new molecules with potential use as medicines. We also use these molecules as tools to address basic science questions. Our main work has involved the engineering of chemokine proteins to produce highly potent HIV entry inhibitors for use in the prevention of transmission of the virus during sexual intercourse. This led to the creation of two spin-offs and has now reached clinical trials, with a Phase 1 study successfully completed in 2020.

The molecules we have discovered act by blocking CCR5, the principal HIV coreceptor, which is also a member of the G protein-coupled receptor (GPCR) superfamily. CCR5 has recently been associated with a number of serious diseases outside of the HIV field, including cancer, neuroinflammation and complications of COVID-19, and there is growing interest in developing CCR5 inhibitors for these indications.

Because they exhibit unusual inhibitory mechanisms that concern modulation of intracellular trafficking of CCR5, our analogs have proven to be very useful tools for studying the cellular and molecular processes that govern both the molecular pharmacology and cell biology of GPCRs. This is the major basic science angle of the group’s research.

In addition, we have combined our expertise in chemistry- and molecular biology-based protein engineering with our knowledge of GPCR molecular pharmacology to develop a set of technologies that can be used to discover highly potent modulators of target GPCRs based on analogs of their natural peptide and protein ligands. This work is the main focus of our applied research, carried out as part of a collaboration agreement with Orion Biotechnology.

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