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Evaluating the transduction efficiency of systemically delivered AAV vectors in the rat nervous system. Front Neurosci 2023;17:1001007

Date

02/10/2023

Pubmed ID

36755734

Pubmed Central ID

PMC9899837

DOI

10.3389/fnins.2023.1001007

Scopus ID

2-s2.0-85147436634 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

Gene delivery or manipulation with viral vectors is a frequently used tool in basic neuroscience studies. Adeno-associated viruses (AAV) are the most widely used vectors due to their relative safety and long-term efficacy without causing overt immunological complications. Many AAV serotypes have been discovered and engineered that preferentially transduce different populations of neurons. However, efficient targeting of peripheral neurons remains challenging for many researchers, and evaluation of peripheral neuron transduction with AAVs in rats is limited. Here, we aimed to test the efficiency of systemic AAVs to transduce peripheral neurons in rats. We administered AAV9-tdTomato, AAV-PHP.S-tdTomato, or AAV-retro-GFP systemically to neonatal rats via intraperitoneal injection. After 5 weeks, we evaluated expression patterns in peripheral sensory, motor, and autonomic neurons. No significant difference between the serotypes in the transduction of sensory neurons was noted, and all serotypes were more efficient in transducing NF200 + neurons compared to smaller CGRP + neurons. AAV-retro was more efficient at transducing motor neurons compared to other serotypes. Moreover, PHP.S was more efficient at transducing sympathetic neurons, and AAV-retro was more efficient at transducing parasympathetic neurons. These results indicate that specific AAV serotypes target peripheral neuron populations more efficiently than others in the neonatal rat.

Author List

Yang OJ, Robilotto GL, Alom F, Alemán K, Devulapally K, Morris A, Mickle AD

Author

Aaron D. Mickle PhD Associate Professor in the Physiology department at Medical College of Wisconsin