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

可注射给药系统修复缺血性中风后的血脑屏障

• 批准号: 10702097
• 负责人: Jordan Taylor Moore
• 金额: $ 8.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702097
• 关键词: Alzheimer' s Disease; Architecture; Atrophic; Award; Axon; Biomedical Engineering; Bioreactors; Blood - brain barrier anatomy; Blood Vessels; Brain-Derived Neurotrophic Factor; Cell Reprogramming; Cell Therapy; Cells; Central Nervous System; Cerebral Palsy; Chromosome Mapping; Cues; Data; Development; Drug Delivery Systems; Effectiveness; Electroporation; Engineering; Environment; Experimental Designs; Foundations; Functional disorder; Gene Delivery; Genes; Genetic; Goals; Growth; Health; Histologic; Immune response; Injectable; Injury; Intervention; Ischemic Stroke; Knowledge; Lead; Leadership; Left; Manuscripts; Mediating; Mentors; Mentorship; Methods; Modeling; Molecular; Motivation; Motor Neurons; Mus; Muscle; Muscle Cells; Natural regeneration; Nerve; Nerve Degeneration; Nerve Regeneration; Nervous System Physiology; Neurites; Neurodevelopmental Disorder; Neuromuscular Junction; Neurons; Ohio; Organ; Outcome; Peripheral Nerves; Peripheral nerve injury; Phase; Population; Positioning Attribute; Postdoctoral Fellow; Predisposition; Preparation; Quality of life; Recovery of Function; Research; Research Personnel; Research Project Grants; Role; STEM field; Science; Site; Skeletal Muscle; Spinal Ganglia; Stroke; System; Technical Expertise; Testing; Therapeutic; Tissues; Training; Universities; Vascular System; Vertebral column; Viral Vector; Work; Writing; Youth; age related; angiogenesis; axon regeneration; community involvement; developmental neurobiology; doctoral student; functional restoration; gene therapy; healing; improved; injured; innovation; loss of function; meter; motor function improvement; nanochannel; nanomedicine; nanotransfection; nerve injury; nerve repair; neural; neurodevelopment; neurogenesis; neuromuscular; neuromuscular function; neuronal cell body; neurovascular; non-viral gene delivery; peripheral nerve regeneration; plasmid DNA; posters; pre-doctoral; precision medicine; preservation; programs; regeneration function; reinnervation; repaired; response; scaffold; sciatic nerve injury; skills; tenure track; vascular injury

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.

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，从脊柱分支，可以延伸到一米远。周围神经损伤 是一种常见的现象，在大多数情况下可以很容易地治愈。然而，18英寸以外的器官 从神经体，是非常容易受到不良的再神经支配的结果和长期的治疗。主 其原因是轴突的生长速度慢（1- 2 mm/天或1英寸/月）。一些组织，如 骨骼肌，可以保持18-24个月的神经再生准备。然而，目前的干预战略 是有限的，大多数伤害是留给自然解决。该应用程序旨在开发一种能够 促进更快的神经突生长，并保持肌肉处于健康状态，直到可以发生神经再生。 本申请集中于非病毒基因货物的组织纳米转染介导的递送，以诱导表达。 分子变化和重新编程细胞。将货物运送到受伤部位的能力 通过精确医学方法，为基于基因和细胞的治疗提供超越神经损伤的途径。 F99阶段的完成为未来的发展奠定了坚实的知识、技术和专业基础。 博士后（K 00）阶段。在K 00阶段，了解细胞和基因如何- 基于治疗影响神经发育和神经退行性疾病将发展知识， 专业知识和技能是成为独立调查员所必需的。