Retrograde gene transfer into neural pathways mediated by adeno-associated virus (AAV)-AAV receptor interaction

Hiromi Sano, Kenta Kobayashi, Nozomu Yoshioka, Hirohide Takebayashi, Atsushi Nambu

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Background: Viral vector systems delivering transgenes in the retrograde direction through axons to neural cell bodies are powerful experimental tools for the functional analysis of specific neural pathways. Generally, the efficiency of viral vector-mediated retrograde gene transfer depends on the expression of requisite viral receptors in neural pathways projecting to the viral vector-injected regions. This is known as viral tropism and can limit the utility of retrograde viral vectors. The adeno-associated virus (AAV) vector has become an increasingly popular platform for gene delivery to neural cells in vivo, and it is therefore meaningful to develop a new type of retrograde gene transfer approach based on a tropism-free AAV vector system. New Method: The wild-type or mutant receptor gene of AAV was expressed to mitigate AAV tropism. Results: Efficient AAV vector-mediated retrograde gene transfer was observed in diverse neural pathways by expression of the AAV receptor (AAVR) gene. Moreover, the expression of a minimal mutant of AAVR (miniAAVR), which maintains binding potential to AAV, demonstrated efficient retrograde gene expression comparable to that of AAVR. Comparison with Existing Methods: The utility of existing AAV vector-mediated retrograde gene delivery methods is sometimes limited by tropism. Our newly developed AAV-AAVR and AAV-miniAAVR interaction approaches enabled efficient retrograde gene transfer into various neural pathways by mitigating tropism. Conclusions: AAV-AAVR and AAV-miniAAVR interaction approaches enabled us to induce efficient retrograde gene expression in targeted neural pathways and provide a powerful tool for analyzing specific neural pathways.

Original languageEnglish
Article number108887
JournalJournal of Neuroscience Methods
Volume345
DOIs
Publication statusPublished - 01-11-2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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