Avery C. Hunker

Abstract Adeno-associated viruses (AAVs) are preferred gene therapy vectors because of their versatility, durability and safety profile. Here, we demonstrate extensive chimerism, manifesting as pervasive barcode swapping, among complex recombinant AAV (rAAV) libraries that are packaged as a pool. The observed chimerism is length and homology dependent but capsid independent, in some cases affecting the majority of packaged rAAV genomes.

Keywords epigenetics transcriptomics enhancer cell type neocortex AAV transgenic recombinase mouse human Introduction To understand how the brain works, we need to establish the structure-function relationships between the units that comprise it and the outputs of its activity.1 One approach is to gain experimental access to each building block (e.g., a cell type) and manipulate it to observe effects on an animal’s physiology and behavior.2,3,4 Historically, the definition of building blocks...

Abstract Cis-acting regulatory enhancer elements are valuable tools for gaining cell type-specific genetic access. Leveraging large chromatin accessibility atlases, putative enhancer sequences can be identified and deployed in adeno-associated virus (AAV) delivery platforms. However, a significant bottleneck in enhancer AAV discovery is charting their detailed expression patterns in vivo, a process that currently requires gold-standard one-by-one testing.