Retrograde gene transfer into neural pathways mediated by adeno-associated virus (AAV)-AAV receptor interaction.,Journal of Neuroscience Methods

当前位置： X-MOL 学术 › J. Neurosci. Methods › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Retrograde gene transfer into neural pathways mediated by adeno-associated virus (AAV)-AAV receptor interaction.
Journal of Neuroscience Methods ( IF 2.7 ) Pub Date : 2020-07-30 , DOI: 10.1016/j.jneumeth.2020.108887
Hiromi Sano ₁ , Kenta Kobayashi ₂ , Nozomu Yoshioka ₃ , Hirohide Takebayashi ₃ , Atsushi Nambu ₄

Affiliation

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.

中文翻译：

逆行基因转移到由腺相关病毒（AAV）-AAV受体相互作用介导的神经通路中。

背景

病毒载体系统通过轴突将逆转基因传递到神经细胞体，是用于特定神经途径功能分析的强大实验工具。通常，病毒载体介导的逆行基因转移的效率取决于投射到病毒载体注射区的神经途径中必需病毒受体的表达。这被称为病毒嗜性，并且可能限制逆行病毒载体的效用。腺相关病毒（AAV）载体已成为在体内向神经细胞传递基因的日益流行的平台，因此，开发一种基于无向性的AAV载体系统的新型逆行基因转移方法具有重要意义。