Drug delivery; drug platforms

A Cas9 ortholog derived from Campylobacter jejuni could enable the use of AAV vectors to deliver CRISPR-based gene therapies. The 984-residue C. jejuni ortholog is smaller than the Cas9 enzymes from Staphylococcus aureus (1,053 residues) or S. pyogenes (1,368 residues) conventionally used for CRISPR gene editing, allowing it to be packaged along with a guide RNA (gRNA) and a fluorescent marker gene into an AAV vector. In a mouse model of laser-induced age-related macular degeneration (AMD), intravitreal injection of an AAV vector encoding the ortholog and a gRNA targeting vascular endothelial growth factor A (VEGF-A) or hypoxia-inducible factor 1 α (HIF1A; HIF1α) decreased the area of choroidal neovascularization compared with no treatment. Next steps could include testing AAVs encoding the C. jejuni Cas9 ortholog and gRNAs to deliver gene therapies in other animal models of disease.

Applied Genetic Technologies Corp. and Biogen Inc. has XLRS (rAAV2tYF-CB-hRS1), an AAV vector delivering retinoschisis X-linked juvenile 1 (RS1; XLRS1), in Phase I/II testing for AMD...