Protein Engineering for Therapy and Diagnosis

Detection of pathological conformations of tau and other amyloid proteins has enormous power for diagnosis and therapy. We have defined epitopes and local protein conformational changes in tau that are associated with its amyloid conformation. We have used this knowledge to design antibodies that are highly specific for “seed-competent” forms of tau, and to create epitopes for active vaccination. This could form the basis of novel immunotherapy for tauopathies.

In parallel, we have adapted the yeast-based nanobody expression system first reported by the Kruze lab (Harvard) to engineer small, single-chain antibodies derived from camelid species, termed nanobodies, that selectively bind pathological tau. Nanobodies have enormous potential, as they can be fused to useful genes for imaging, targeted protein degradation, or cellular uptake.

We are also developing standard antibodies and nanobodies to identify pathological conformations of amyloid proteins in biofluids, and even in brain using PET imaging.

Overall, we seek to translate our knowledge of defined tau structures into better ways to detect incipient tauopathy and intervene with mechanism-based therapy.