Translational AAV Delivery Platform to the Brain

大脑转化 AAV 传递平台

基本信息

批准号：
8696895
负责人：
Krystof S Bankiewicz
金额：
$ 55.35万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8696895
关键词：
Address Axonal Transport Behavior Brain Brain Stem Brain region Cannulas Cellular Tropism Clinic Clinical Clinical Trials Communities Corpus striatum structure Development Disease Employee Strikes FDA approved Gene Delivery Gene Transduction Agent Gray unit of radiation dose Human Image Immune response Infusion procedures Investments Island Magnetic Resonance Imaging Monitor Movement Multiple Sclerosis Nature Neurologic Neurons Neurosurgeon Oligodendroglia Patients Performance Primates Procedures Property Protocols documentation Relative (related person)Research Personnel Resources Safety Scientist Serotyping Specificity Structure System Techniques Technology Thalamic structure Therapeutic Therapeutic Agents Tracer Viral Vector adeno-associated viral vector anterograde transport base clinically relevant design empowered gene therapy gray matter improved in vivo millimeter nervous system disorder neurosurgery nonhuman primate programs putamen response transgene expression vector white matter

项目摘要

DESCRIPTION (provided by applicant): To advance neurological gene therapy applications into the clinic there is an urgent need to improve our understanding of gene delivery vectors, with particular emphasis on distribution and safety after direct brain delivery. While AAV2 currently dominates clinical development, alternative AAV serotypes may be better suited for some applications. The recent game-changing development of image-guided delivery techniques provides opportunity to accurately compare different vectors after direct brain delivery. Accordingly we aim to investigate the distribution and immune responses of 5 AAV serotypes (AAV1, 2, 5, 8 and 9) after confined delivery to grey or white matter structures in the non-human primate (NHP) brain. This in-depth assessment of AAV vectors will provide investigators with scientific rational for selecting a specific vector for a particular neurological application.

描述（由申请人提供）：为了将神经基因治疗应用推向临床，迫切需要提高我们对基因递送载体的理解，特别强调直接脑递送后的分布和安全性。虽然 AAV2 目前主导临床开发，但替代 AAV 血清型可能更适合某些应用。图像引导递送技术的最新发展改变了游戏规则，为直接大脑递送后准确比较不同载体提供了机会。因此，我们的目标是研究 5 种 AAV 血清型（AAV1、2、5、8 和 9）在限制递送至非人灵长类动物 (NHP) 大脑灰质或白质结构后的分布和免疫反应。这种对 AAV 载体的深入评估将为研究人员为特定神经学应用选择特定载体提供科学依据。