The University of British Columbia

Purpose

Neurological disorders affect up to 10% of Canadians, and few treatment options exist. Current understanding of disease pathogenesis suggests that protein replacement or supplementation is an attractive therapeutic approach. However, the development of protein biologics for the brain is marred by two key problems: spatial distribution across the BBB and short protein half-lives. The project will investigate the delivery of protein biologics to the brain using an in situ ‘Bioreactor’ approach. Using lipid nanoparticles encapsulating messenger RNA (LNP-mRNA), a subset of brain cells are instructed to produce and secrete therapeutic proteins continually over the lifespan of stably-modified RNA. Using LNPs that cross the BBB, this unique bioreactor approach could deliver proteins with brain-wide diffusion. This approach only requires limited cell transfection rate, has low cell-specific tropism requirements, and can be adapted to produce proteins for different indications. It therefore represents a platform-enabling translatable strategy for novel nanomedicines for a range of neurological diseases.