Injectable drug-delivery system to repair the blood-brain-barrier after ischemic stroke

项目摘要 神经系统的正常运作对我们的生活质量非常重要。神经 在我们的身体内，从脊柱发出分支，可以延伸到一米远。周围神经损伤 这是一种常见现象，并且在大多数情况下很容易治愈。然而，末端器官超出约 18 英寸远 来自神经体的，非常容易受到神经支配不良结果和长期损害的影响。一个主要 其原因是轴突生长缓慢（1-2 毫米/天或 1 英寸/月）。一些组织，例如 骨骼肌，可以在 18-24 个月内保持神经支配的准备状态。然而，目前的干预策略 伤害是有限的，大多数伤害都会自然消退。该应用程序旨在开发一种能够 促进神经突更快生长并保持肌肉处于健康状态，直到神经支配发生。 该应用重点关注组织纳米转染介导的非病毒基因货物的递送以诱导 分子变化和重新编程细胞。能够将货物本地运送到受伤地点 通过精准医学方法进行基于基因和细胞的治疗，超越神经损伤的途径。 F99阶段的完成为F99阶段奠定了坚实的智力、技术和专业基础 该奖项的博士后（K00）阶段。在 K00 阶段，培训了解细胞和基因如何 基于疗法影响神经发育和神经退行性疾病将发展知识， 成为独立调查员所必需的专业知识和技能。

PROJECT ABSTRACT Appropriate functioning of the nervous system is tremendously important to our quality of life. The nerves within our body branch from the spinal column and can extend up to one meter away. Peripheral nerve injuries are a common occurrence and can readily heal in most cases. However, end-organs beyond ~18 inches away from the nerve body, are highly susceptible to poor reinnervation outcomes and long-term detriments. A main reason for this being the slow growth rate of the axons (1-2mm/day or 1 inch/month). Some tissues, such as skeletal muscle, can remain ready for reinnervation for 18-24 months. However, current intervention strategies are limited, and most injuries are left to resolve naturally. This application aims to develop a strategy capable of promoting quicker neurite outgrowth and preserving the muscle in a healthy state until reinnervation can occur. This application focuses on tissue-nanotransfection mediated delivery of non-viral gene cargo to induce molecular changes and to reprogram cells. The ability to deliver cargos locally to the site of injury opens avenues beyond nerve injury for gene and cell-based therapeutics with a precision medicine approach. Completion of the F99 phase sets a strong intellectual, technical and professional foundation for the postdoctoral (K00) phase of this award. During the K00 phase, training in understanding how cell and gene- based therapies impact neurodevelopmental and neurodegenerative conditions will develop knowledge, expertise, and skills essential to becoming an independent investigator.