Seminars

Abstract: 

The central nervous system (CNS) – brain, spinal cord, retina – has often been thought of as the final frontier of medicine. Biologics have the potential to promote tissue regeneration, yet their delivery to the CNS remains challenging. We designed a local delivery strategy to overcome the blood-brain barrier, a series of protein affinity controlled release methods and a novel, re-engineered protein to be more stable than the wildtype. We discovered encapsulation-free protein release – that is proteins do not have to be encapsulated, but rather their release can be controlled by electrostatic affinity interactions [1]. We demonstrate tissue and functional repair with local delivery of an immunomodulatory peptide [2].  The mechanism for this will be described as will the affinity release based on discrete protein-peptide binding partners.  For the latter, we express fusion proteins with Src homology 3 (SH3) and modify our hydrogel delivery vehicle with SH3-binding peptides, thereby controlling release of our protein of interest through the affinity of SH3 and its binding peptides [3].  We achieved success with the potent, yet fragile, chondroitinase abc (ChASE), re-engineered it to be more stable and active [4] and showed tissue and functional repair in models of stroke and spinal cord injury.

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