Overcoming barriers in non-viral gene delivery for neurological applications.
Overcoming barriers in non-viral gene delivery for neurological applications.
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作为一种逆转或阻止各种疾病病理的方法，神经系统疾病的基因治疗引起了人们的极大兴趣。涉及中枢和周围神经系统的典型基因疗法利用腺相关病毒载体，其安全性和制造局限性引起了人们对非病毒载体的广泛研究。虽然早期研究表明这些非病毒载体的功效有限，但对各种载体材料和功能化方法的研究提供了对优化这些非病毒载体的方法的深入了解，以改善所需的特性，例如改善血脑屏障转胞吞作用、改善脑区域灌注、增强神经细胞的细胞摄取和内体逃逸，以及细胞内递送后遗传物质的核转运。研究小组结合使用各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各种临床前应用，用于治疗帕金森病、脑癌和神经元替代的细胞重编程。虽然在设计这些用于神经应用的多功能非病毒载体方面还需要做更多的工作，但大部分基础工作已经完成并在此进行了回顾。研究克服细胞外和细胞内障碍的各种策略，以利用非病毒载体改善神经元应用中的基因传递。
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. Investigation of various strategies to overcome extracellular and intracellular barriers for improved gene delivery in neuronal applications utilizing non-viral vectors.
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影响因子：
3.7
作者：
Bergen, Jamie M.;Park, In-Kyu;Horner, Philip J.;Pun, Suzie H.
通讯作者：
Pun, Suzie H.
影响因子：
14
作者：
Chu, David S. H.;Schellinger, Joan G.;Bocek, Michael J.;Johnson, Russell N.;Pun, Suzie H.
通讯作者：
Pun, Suzie H.
影响因子：
5.6
作者：
Polańska Ż;Pietralik-Molińska Z;Wojciechowska D;Moliński A;Weiss M;Skrzypczak A;Kozak M
通讯作者：
Kozak M
DOI：
10.1073/pnas.92.10.4572
发表时间：
1995-05-09
影响因子：
11.1
作者：
DOWTY, ME;WILLIAMS, P;WOLFF, JA
通讯作者：
WOLFF, JA
一种穿越血脑屏障的非病毒自杀基因传递系统，用于非侵入性胶质瘤靶向治疗
影响因子：
10.8
作者：
Gao, Shiqian;Tian, Huayu;Chen, Xuesi
通讯作者：
Chen, Xuesi