SBF: Delivery of drugs across the BBB using shark VNAR biotools

A Scottish Biologics Facility Project, in collaboration with the KCT: 

Although they posses the ability to bind to specific receptors proteins in the Blood Brain Barrier, monclonal Antibodies (mAbs) are large globular structures (in relative molecular terms) that are not conducive to tissue penetration, and do not lend themselves readily to multiple target formatting. However, a novel class of simple single chain antibodies isolated from the adaptive immune system of sharks (known as VNARs), overcome many of these physical limitations of mAbs, whilst retaining the high specificity and affinity for target. Their simple single chain structure makes them amenable to combinatorial therapy enabling more than one target or biological pathway to be modulated simultaneously. This is a huge driver in current drug design as the complexity of disease pathways and mechanisms are elucidated, the necessity to regulate multiple components becomes imperative. The aim of this project is to construct a VNAR bio-tool, amenable to fusion to other therapeutically relevant drugs, and capable of specifically binding and crossing the BBB to deliver its payload of drugs into the brain. In the last year, work studying the transferrin receptor (TnFR) has shown that hitting a particular epitope facilitated a conformational change in the protein and the active transport of a mAb into the brain (Yu et al, 2011. Sci Transl Med 3 (84)1). Other receptors on the BBB may have similar activities (Glucose Transporters)

Project Team: Professor Andy Porter, Professor Matteo Zanda, Dr Peter Teismann

Funding: MSD SULSA PhD Studentship