An NMIN lecture by Dr. Blair Leavitt (Professor, Department of Medical Genetics & the Department of Medicine, Division of Neurology, The University of British Columbia) and Sarah Thomson (PhD Candidate, The University of British Columbia).
Lipid nanoparticle (LNP)-enabled gene therapy is a promising approach for the treatment of genetic neurological disease. To optimize LNP-enabled nucleic acid delivery for this purpose, we developed an iterative screening strategy using neurons ex vivo to identify unique LNP formulation parameters for siRNA and mRNA delivery. We show LNPs efficiently deliver both cargoes to neurons ex vivo, that formulation potency and toxicity vary with lipid composition and dose, and explore the utility of LNP-mediated CRISPR/Cas9 genome editing in neurons.