Brain delivery of the PrPSc-specific single-chain antibody fragment
Nives Skrlj Department of Biochemistry Chair
Faculty of Chemistry and Chemical Technology
University of Ljubljana
Slovenia
Abstract:
Delivery of therapeutic proteins into tissues and across the blood-brain barrier (BBB) is limited by the size and biochemical properties of the proteins. Efficient delivery across BBB is generally restricted to small, highly lipophilic molecules. However, in the last decades, several peptides that can translocate cell membranes have been identified. Besides, these peptides are capable of internalizing large cargoes and are therefore a powerful biological tool for transporting drugs across cell membranes.Antibody-based immunotherapy might represent an effective treatment for several brain diseases including transmissible spongiform encephalopathies, but unfortunately full-size antibodies do not cross the BBB. The present work describes design and preparation of single-chain antibody fragments (scFvs), specific for the pathological form of the prion protein (PrPSc), where the cell penetrating peptide (CPP) was used as a linker between the two variable domains of the scFv. The intravenously administered recombinant scFv-CPP was successfully delivered to the mouse brain. Our single-chain antibody fragments are of special interest in view of possible therapeutic reagents not only for prion diseases but also for other neurodegenerative diseases.
