Avatar has developed a proprietary protein engineering technology based on the introduction of targeted di-tyrosine (DT) crosslinks, which allows proteins to be locked in desired conformations. We apply this methodology to engineer novel vaccine immunogens that are locked in the conformation that elicits the most potently protective antibody responses.
DT bonds are targeted within protein structures by (i) introducing Tyr substitutions at positions that are in very close structural proximity, and (ii) introducing covalent crosslinks between these Tyr pairs, using a mild enzymatic reaction. DT bonds are introduced after the protein is fully folded, and they create zero-length carbon-carbon bonds that are used to lock the protein irreversibly in its desired conformation, without altering the rest of the molecule. This minimally modifying approach retains the target protein’s structural integrity and confers the following advantages: