Abstract
The options available for genetic modification of cells of the central nervous system (CNS) have greatly increased in the last decade. The current panoply of viral and nonviral vectors provides multifunctional platforms to deliver expression cassettes to many structures and nuclei. These cassettes can replace defective genes, modify a given pathway perturbed by diseases, or express proteins that can be selectively activated by drugs or light to extinguish or excite neurons. This review focuses on the use of canine adenovirus type 2 (CAV-2) vectors for gene transfer to neurons in the brain, spinal cord, and peripheral nervous system. We discuss (1) recent advances in vector production, (2) why CAV-2 vectors preferentially transduce neurons, (3) the mechanism underlying their widespread distribution via retrograde axonal transport, (4) how CAV-2 vectors have been used to address structure/function, and (5) their therapeutic applications.
Highlights
Danila del Rio1†, Bertrand Beucher2†, Marina Lavigne1†, Amani Wehbi1, Iria Gonzalez Dopeso-Reyes1, Isabella Saggio3,4 and Eric J
This review focuses on the use of canine adenovirus type 2 (CAV-2) vectors for gene transfer to neurons in the brain, spinal cord, and peripheral nervous system
Viral vectors will continue to help advance the characterization of brain function, circuitry and neural plasticity
Summary
The options available for genetic modification of cells of the central nervous system (CNS) have greatly increased in the last decade. Combining circuitry data with functional analyses based on the effect of ablation, diseases, infections, or injury of a given population of neurons provides insight into the physiological role of some brain regions (Caeyenberghs et al, 2017). This foundation is being built upon by the advent of gene transfer tools that modify cells at the injection site, modify neurons that synapse to those that are transduced at the injection site (via anterograde transsynaptic transport), or modify neurons that project into the injection site via retrograde transport of the vector. The limitations in gene transfer efficacy are frequently overcome by using novel and modified viral vectors
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