Gao Zhenghong
Mechanical Engineering, The University of Texas at Dallas USA
Nanoscale Adv. 2024 Apr 25;6(12):3009-3028. doi: 10.1039/d3na01125a. eCollection 2024 Jun 11.
The delivery of genes to the central nervous system (CNS) has been a persistent challenge due to various biological barriers. The blood-brain barrier (BBB), in particular, hampers the access of systemically injected drugs to parenchymal cells, allowing only a minimal percentage (<1%) to pass through. Recent scientific insights highlight the crucial role of the extracellular space (ECS) in governing drug diffusion. Taking into account advancements in vectors, techniques, and knowledge, the discussion will center on the most notable vectors utilized for gene delivery to the CNS. This review will explore the influence of the ECS - a dynamically regulated barrier-on drug diffusion. Furthermore, we will underscore the significance of employing remote-control technologies to facilitate BBB traversal and modulate the ECS. Given the rapid progress in gene editing, our discussion will also encompass the latest advances focused on delivering therapeutic editing to the CNS tissue. In the end, a brief summary on the impact of Artificial Intelligence (AI)/Machine Learning (ML), ultrasmall, soft endovascular robots, and high-resolution endovascular cameras on improving the gene delivery to the CNS will be provided.
由于各种生物屏障的存在，将基因递送至中枢神经系统（CNS）一直是一项持续存在的挑战。尤其是血脑屏障（BBB），它阻碍了全身注射药物进入实质细胞，仅有极小比例（<1%）的药物能够通过。最近的科学见解突出了细胞外空间（ECS）在控制药物扩散方面的关键作用。考虑到载体、技术和知识的进步，讨论将聚焦于用于向中枢神经系统进行基因递送的最显著载体。本综述将探讨ECS（一种动态调节的屏障）对药物扩散的影响。此外，我们将强调采用远程控制技术以促进血脑屏障穿越和调节ECS的重要性。鉴于基因编辑的快速进展，我们的讨论还将涵盖专注于向中枢神经系统组织递送治疗性编辑的最新进展。最后，将简要总结人工智能（AI）/机器学习（ML）、超小型软质血管内机器人和高分辨率血管内摄像头对改善向中枢神经系统进行基因递送的影响。
