GENE THERAPY OF BRAIN TUMORS

脑肿瘤的基因治疗

• 批准号: 6277767
• 负责人: VITO G SASSEVILLE
• 金额: $ 7.6万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277767
• 关键词: Mammalia; Primates; animal tissue; biological products; model design /development; nervous system; virus

This subcontract investigates the administration and neuropathogenesis of novel virus vectors (retrovirus, herpes simplex type 1 and herpes-amplicon) in nonhuman primates. Initially, we used rhesus monkeys to examine the infiltration of a herpesvirus vector after intracerebral injection (using a novel stereotactic micro-injection apparatus) and the host response to this vector. To date we have examined two animals both animals were given general anesthesia, placed in a sterotactic apparatus, and craniotomies performed under sterile conditions. Using a micro-injection apparatus four 26 gauge needles placed 5 mm apart from one another were inserted 10 mm into the right frontal cortex. Herpesvirus (a total of 1 X 109 pfu in 100 ul/ injection) were injected over 120 minutes. After injection, needles and stereotactic apparatus were removed and the craniotomy sites were closed by routine surgical procedures. One animal was euthanized and examined 48 hours post-injection and one 14 days post-injection. Both animals had complete post-mortem examinations. Both animals had focally extensive malacia at the site of injection. Viral protein was detected in inflammatory cells and occasional neurons in the animal euthanized 48 hours after exposure to the HSV-1 mutant, but not in the animal euthanized and examined at 14 days post injection. Our preliminary studies have shown that naive rhesus monkeys (rhesus herpesvirus B negative) can be infected with HSV-1 and mount an antibody response to HSV-1, but do not develop generalized. Although the rhesus monkey is a suitable model for certain HSV-1 studies, to adequately assess the safety of HSV-1 mutants in man, we are currently using owl monkeys (Aotus sp.), which are susceptible to generalized HSV-1 infection. Presently, two owl monkeys have been infected with HSV-1 mutants (108 pfu) intracerebrally (as described above) and euthanized and examined at four and twelve weeks post infection. Neither viral protein nor significant histopathologic changes were detected in CNS and other tissues examined. Additional animals will be investigated in year three of this proposal.

这位检察官调查了行政部门， 新型病毒载体（逆转录病毒、单纯疱疹病毒）的神经发病机制 1型和疱疹-扩增子）。 最初，我们使用 恒河猴，以检查疱疹病毒载体的渗透 脑内注射后（使用新型立体定向 微注射装置）和宿主对该载体的应答。 到 我们检查了两只动物， 麻醉，放置在立体定向装置中，以及开颅术 在无菌条件下进行。 使用微量注射装置 插入四个26号针，彼此间隔5 mm 右额叶皮层10毫米处。 疱疹病毒（共1 X 109 PFU，100 μ l/注射）在120分钟内注射。 后 注射，针和立体定向装置被移除， 通过常规外科手术闭合开颅部位。 一 注射后48小时对动物实施安乐死并进行检查， 注射后天数。 两只动物都有完整的尸检 考试 两只动物在该部位均有局灶性广泛软化 注射。 在炎症细胞中检测到病毒蛋白， 在暴露后48小时处死的动物中的偶然神经元 HSV-1突变体，但在14岁时安乐死和检查的动物中没有 注射后天数。 我们的初步研究表明， 恒河猴（恒河猴疱疹病毒B阴性）可感染 HSV-1，并产生对HSV-1的抗体应答，但不发展 一般化。 尽管恒河猴是一个合适的模型， 某些HSV-1研究，以充分评估HSV-1的安全性 人类的突变体，我们目前正在使用猫头鹰猴（Aotus sp.），这 易受HSV-1感染。 目前，两只猫头鹰 猴感染HSV-1突变体（108 pfu） 脑内注射（如上所述），安乐死并在 感染后四周和十二周。 病毒蛋白和 在CNS和其他组织中检测到显著的组织病理学变化 检查组织。 今年将对更多动物进行调查 三是这个提案。