Zhou Livia, Wang Yafeng, Xu Yiran, Zhang Yaodong, Zhu Changlian
Henan Neurodevelopment Engineering Research Center for Children, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital, Zhengzhou 450018, China.
Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Mol Ther Methods Clin Dev. 2024 Oct 16;32(4):101357. doi: 10.1016/j.omtm.2024.101357. eCollection 2024 Dec 12.
Pediatric monogenetic diseases encompass a spectrum of debilitating neurological disorders that affect infants and children, often resulting in profound cognitive and motor impairments. Gene replacement therapy holds immense promise in addressing the underlying genetic defects responsible for these conditions. Adeno-associated virus (AAV) vectors have emerged as a leading platform for delivering therapeutic genes due to their safety profile and ability to transduce various cell types, including neurons. This review highlights recent advancements in AAV-mediated gene replacement therapy for pediatric monogenetic diseases, focusing on key preclinical and clinical studies. We discuss various strategies to enhance transduction efficiency, target specificity, and safety. Furthermore, we explore challenges such as immune responses, along with innovative approaches to overcome these obstacles. Moreover, we examine the clinical outcomes and safety profiles of AAV-based gene therapies in pediatric patients, providing insights into the feasibility and efficacy of these interventions. Finally, we discuss future directions and potential avenues for further research to optimize the therapeutic potential of AAV-delivered gene replacement therapy for pediatric encephalopathies, ultimately aiming to improve the quality of life for affected individuals and their families.
儿科单基因疾病包括一系列影响婴幼儿的使人衰弱的神经障碍，常常导致严重的认知和运动功能障碍。基因替代疗法在解决导致这些病症的潜在基因缺陷方面具有巨大潜力。腺相关病毒（AAV）载体因其安全性以及转导包括神经元在内的各种细胞类型的能力，已成为递送治疗性基因的主要平台。本综述重点介绍了AAV介导的儿科单基因疾病基因替代疗法的最新进展，着重于关键的临床前和临床研究。我们讨论了提高转导效率、靶向特异性和安全性的各种策略。此外，我们探讨了诸如免疫反应等挑战，以及克服这些障碍的创新方法。此外，我们研究了基于AAV的基因疗法在儿科患者中的临床结果和安全性概况，深入了解这些干预措施的可行性和疗效。最后，我们讨论未来的方向以及进一步研究的潜在途径，以优化AAV递送的基因替代疗法对儿科脑病的治疗潜力，最终目标是改善受影响个体及其家庭的生活质量。
