Project Overview

Challenge: Delivery of therapeutic proteins to the brain has been a longstanding barrier to CNS drug
development. Protein replacement or supplementation strategies hold promise for multiple brain diseases,
from enzyme-replacement for neuronopathic lysosomal disorders, to growth factor supplementation for
neurodegeneration, to cytokine immunotherapy for brain cancers. However, most brain diseases remain
poorly treated in part due to the inability to deliver proteins to the brain with a disease-appropriate
biodistribution.

Solution: We address the brain protein delivery challenge using lipid nanoparticle (LNP) to bring to brain
cells the RNA blueprint that encodes for a therapeutic protein. Our LNP-RNA products instruct the host cell
to secrete a desired protein that then diffuses broadly throughout the brain, effectively harnessing brain
cells to become ‘protein factories’ within the brain itself.

Expected achievements/Impact: The co-funders CereCura Nanotherapeutics Inc. and RNA
Technologies and Therapeutics Inc. have shown the strategy is viable in rodents, demonstrating this
versatile technology can deliver multiple proteins with unprecedented spatiotemporal distribution in the
brain. Leveraging the expertise of Dr Tremblay and the Université Laval Translational Neurosurgery
Laboratory in optimizing genetic drug delivery to non-human primate (NHP) brains and that of Dr MacVicar
at UBC in mouse models of neurological diseases, our group will 1) demonstrate the feasibility of LNPRNA-
induced protein delivery to NHP brain, 2) optimize the RNA cargo of a lead candidate drug product
using in vitro models and 3) validate its therapeutic in a specific disease use case (neuronopathic lysosomal
disease). Key translational validation of the technology and development of a lead drug asset will attract
investors and clinical partners to ensure further commercial development of a made-in-Canada
transformative solution to CNS disorders. We combine the burgeoning Quebec RNA therapeutics industry
with the Vancouver LNP development hub, to bring closer to first-in-human trials a clinically- and
commercially-viable therapeutic approach, bringing hope to Quebecers and Canadians suffering from
debilitating brain diseases.

Principal Investigator

Sébastien Tremblay , Université Laval

Team Members

Brian MacVicar, University of British Columbia

Partners and Donors

CQDM

RNA T&T

CereCura Nanotherapeutics