Page 35 - IBRO_RNA School_Abstract Book

Building a Toolbox of Enhancer-AAVs for Cell Population-Se-

lective Gene Expression Across Species

Boaz P. Levi

Allen Institute for Brain Science, Washington, U.S

Selective transgene expression is critical to the study of brain cell types and
their roles in circuit function and disease. Unfortunately, few tools have been
validated that allow labeling of defined cell subclasses and types across mammalian
species. To enable such labeling, we are generating a set of new AAV
vectors that drive transgene expression in defined cell subclasses. We undertook a
systematic screen to find enhancer elements capable of targeting AAV

expression to major neocortical cell populations. Our strategy leverages single cell-
resolution transcriptomic and epigenetic analyses of brain cells from mouse and human,
followed by in vivo testing in mouse and NHP; and ex vivo testing in NHP and
human. These studies generated a diverse collection of enhancer-AAV vectors that
specifically target neocortical neuronal and glial cell populations across species. Our
growing toolbox of enhancer-AAVs for selective transgene expression will be key to
better understand the roles of cell subclasses and types in brain function across species.