Retrograde gene transfer into neural pathways mediated by adeno-associated virus (AAV)-AAV receptor interaction
Retrograde gene transfer into neural pathways mediated by adeno-associated virus (AAV)-AAV receptor interaction
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DOI：
10.1016/j.jneumeth.2020.108887
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发表时间：
2020-11-01
影响因子：
3
通讯作者：
Nambu, Atsushi
中科院分区：
文献类型：
--
作者：
Sano, Hiromi;Kobayashik, Kenta;Nambu, Atsushi
背景资料：病毒载体系统将转基因以逆行方向通过轴突传递到神经细胞体，是用于特定神经通路的功能分析的有力实验工具。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域的神经通路中必需的病毒受体的表达。这被称为病毒向性，并且可以限制逆行病毒载体的效用。腺相关病毒（adeno-associated virus，AAV）载体已成为一种越来越受欢迎的体内基因转移平台，因此开发一种基于无向性AAV载体系统的新型逆行基因转移方法具有重要意义。新方法：表达野生型或突变型AAV受体基因以减轻AAV的向性。通过表达AAV受体（AAVR）基因，在多种神经通路中观察到有效的AAV载体介导的逆行基因转移。此外，表达的AAVR（miniAAVR），它保持结合潜力的AAV的最小突变体，表现出有效的逆行基因表达的AAVR.Comparison与现有的方法：现有的AAV载体介导的逆行基因传递方法的效用有时是有限的向性。我们新开发的AAV-AAVR和AAV-miniAAVR相互作用方法通过减轻向性使高效的逆行基因转移到各种神经通路中。结论：AAV-AAVR和AAV-miniAAVR相互作用方法使我们能够在靶向神经通路中诱导高效的逆行基因表达，并为分析特定神经通路提供了有力的工具。
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.