Retrograde capabilities of adeno-associated virus vectors in the central nervous system

Abstract

Adeno-associated virus (AAV) vectors delivered at the axonal terminals can be retrogradely transported toward neuronal cell bodies throughout the axons. This retrograde phenomenon can serve as a powerful tool for experiments and gene therapy using AAVs. The advantages of using AAV vectors delivered retrogradely are greater cellular specificity, high transduction efficiency, increased safety, and absence of cytotoxicity. The numerous axonal projections in the nervous system provide a neuronal network for the convenient and widespread distribution of viral vectors between adjacent brain structures and over long distances. The retrograde efficiency of AAVs in the neurons of the central nervous system (CNS) depends on AAV serotype, the region of injection, and the type of neurons. In this review, we describe AAV serotypes and their retrograde transport properties after injection and discuss brain structures or types of cells that are targeted for retrograde transport. In particular, AAV serotypes 2, 5, 8, 9, rh10, and PHP.eB are extensively reviewed as they demonstrate retrograde transport potential suitable for use in gene therapy applications.