Division of Pharmacoengineering and Molecular Pharmaceutics, Department of Pharmaceutical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Division of Pharmacoengineering and Molecular Pharmaceutics, Department of Pharmaceutical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Curr Opin Pharmacol. 2017 Jun;34:56-63. doi: 10.1016/j.coph.2017.07.001. Epub 2017 Jul 22.
The use of recombinant adeno-associated viruses (rAAVs) is highly prevalent in musculoskeletal gene therapies due to their versatility, high transduction efficiency, natural tropism and vector genome persistence for years. As the largest organ in the body, treatment of skeletal muscle for widespread and sufficient therapeutic gene expression is highly challenging. In addition to disease-specific hurdles, vector genome loss, off-target gene transfer and immune responses to treatment can diminish the overall benefit of rAAV therapies. A variety of approaches have been developed to overcome these challenges and improve musculoskeletal targeting of rAAVs. This review focuses on recent advancements and remaining obstacles in creating optimal rAAV-based therapies for musculoskeletal application.
腺相关病毒（rAAV）的使用在肌肉骨骼基因治疗中非常普遍，因为它们具有多功能性、高转导效率、天然趋向性和载体基因组多年持续存在的特点。作为人体最大的器官，治疗骨骼肌以实现广泛而充分的治疗性基因表达极具挑战性。除了特定疾病的障碍外，载体基因组丢失、靶外基因转移和对治疗的免疫反应都会降低 rAAV 治疗的整体效果。已经开发了多种方法来克服这些挑战，并提高 rAAV 在肌肉骨骼中的靶向性。本综述重点介绍了在创建用于肌肉骨骼应用的最佳 rAAV 治疗方法方面的最新进展和仍然存在的障碍。
