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AAV Targeting of Glial Cell Types in the Central and Peripheral Nervous System and Relevance to Human Gene Therapy
Frontiers in Molecular Neuroscience ( IF 4.8 ) Pub Date : 2020-12-11 , DOI: 10.3389/fnmol.2020.618020
Simon J. O’Carroll , William H. Cook , Deborah Young

Different glial cell types are found throughout the central (CNS) and peripheral nervous system (PNS), where they have important functions. These cell types are also involved in nervous system pathology, playing roles in neurodegenerative disease and following trauma in the brain and spinal cord (astrocytes, microglia, oligodendrocytes), nerve degeneration and development of pain in peripheral nerves (Schwann cells, satellite cells), retinal diseases (Müller glia) and gut dysbiosis (enteric glia). These cell type have all been proposed as potential targets for treating these conditions. One approach to target these cell types is the use of gene therapy to modify gene expression. Adeno-associated virus (AAV) vectors have been shown to be safe and effective in targeting cells in the nervous system and have been used in a number of clinical trials. To date, a number of studies have tested the use of different AAV serotypes and cell-specific promoters to increase glial cell tropism and expression. However, true glial-cell specific targeting for a particular glial cell type remains elusive. This review provides an overview of research into developing glial specific gene therapy and discusses some of the issues that still need to be addressed to make glial cell gene therapy a clinical reality.



中文翻译:

AAV靶向中枢和周围神经系统中的胶质细胞类型及其与人类基因治疗的相关性

在整个中枢(CNS)和周围神经系统(PNS)中发现了不同的神经胶质细胞类型,它们在其中具有重要的功能。这些细胞类型也参与神经系统病理,在神经退行性疾病中起作用,并在脑和脊髓(星形细胞,小胶质细胞,少突胶质细胞)受到创伤,神经变性和周围神经疼痛发展(施万恩细胞,卫星细胞)中起作用,视网膜疾病(Müller胶质细胞)和肠道营养不良(肠胶质细胞)。这些细胞类型都已被提议作为治疗这些疾病的潜在靶标。靶向这些细胞类型的一种方法是使用基因疗法来修饰基因表达。腺相关病毒(AAV)载体已被证明可安全有效地靶向神经系统中的细胞,并已用于许多临床试验中。迄今为止,许多研究已经测试了使用不同的AAV血清型和细胞特异性启动子来增加神经胶质细胞的嗜性和表达。然而,针对特定神经胶质细胞类型的真正神经胶质细胞特异性靶向仍然难以捉摸。这篇综述概述了发展神经胶质细胞特异性基因疗法的研究,并讨论了使神经胶质细胞基因疗法成为临床现实仍需要解决的一些问题。

更新日期:2021-01-11
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