Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Nanoscale. 2022 Mar 10;14(10):3698-3719. doi: 10.1039/d1nr06939j.
Gene therapy for neurological disorders has attracted significant interest as a way to reverse or stop various disease pathologies. Typical gene therapies involving the central and peripheral nervous system make use of adeno-associated viral vectors whose questionable safety and limitations in manufacturing has given rise to extensive research into non-viral vectors. While early research studies have demonstrated limited efficacy with these non-viral vectors, investigation into various vector materials and functionalization methods has provided insight into ways to optimize these non-viral vectors to improve desired characteristics such as improved blood-brain barrier transcytosis, improved perfusion in brain region, enhanced cellular uptake and endosomal escape in neural cells, and nuclear transport of genetic material post- intracellular delivery. Using a combination of various strategies to enhance non-viral vectors, research groups have designed multi-functional vectors that have been successfully used in a variety of pre-clinical applications for the treatment of Parkinson's disease, brain cancers, and cellular reprogramming for neuron replacement. While more work is needed in the design of these multi-functional non-viral vectors for neural applications, much of the groundwork has been done and is reviewed here.
基因治疗在神经紊乱领域的应用引起了广泛关注，它为逆转或阻止各种疾病病理提供了一种可能的途径。涉及中枢和外周神经系统的典型基因疗法利用腺相关病毒载体，但这些载体的安全性令人质疑，且在制造方面存在局限性，这促使人们对非病毒载体进行了广泛的研究。尽管早期的研究表明这些非病毒载体的疗效有限，但对各种载体材料和功能化方法的研究为优化这些非病毒载体以改善所需特性提供了思路，例如提高血脑屏障的转胞吞作用、改善脑区灌注、增强神经细胞的细胞摄取和内体逃逸，以及细胞内递送至细胞核内的遗传物质的核转运。研究小组采用了多种策略来增强非病毒载体，设计了多功能载体，这些载体已成功用于多种帕金森病、脑癌和神经细胞替代的细胞重编程的临床前应用。虽然神经应用的多功能非病毒载体的设计还需要做更多的工作，但这里已经对大部分基础工作进行了回顾。
