Unraveling kidney clearance mechanisms of nanobodies (FWOAL951)

It has been shown that nanobodies (Nbs), small antigen-binding fragments derived from special Camelid-antibodies, possess exceptional characteristics to act as molecular tracers for various diagnostic and therapeutic clinical applications. However, the renal clearance and in particular the retention of Nbs in the kidneys remains a major limitation both in terms potential toxicity and non- specific accumulation causing background signals. This problem has so far not been addressed properly, and advances mostly rely on accidental observations resulting from trial-and-error approaches. The full comprehension of the mechanisms involved in the renal processing of Nbs will provide fundamental insights and new research opportunities to tackle this problem.
The project will be led by Prof. Hernot and Prof. Xavier from the Vrije Universiteit Brussel, and will be performed in collaboration with Prof. Devuyst (University of Zurich). Their complementary expertise in respectively the design and in vivo evaluation of Nb-tracers, (radio)chemical modifications of Nbs and renal physiology offers the unique opportunity to investigate and alter the fate of Nbs in the kidneys. They propose to exploit various state-of-the-art technologies to precisely locate Nbs within the renal anatomy, study the metabolization of Nbs and assess in detail their potential nephrotoxicity. This information is expected to permit the rational design of Nbs and Nb-tracers that show fast elimination from the kidneys

Keywords:drug discovery

Disciplines:Drug discovery and development not elsewhere classified, Medical imaging and therapy not elsewhere classified, Pharmacokinetics, Urology and nephrology not elsewhere classified