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.

该分包合同调查了政府和 新型病毒载体的神经病发生（逆转录病毒，单纯疱疹 非人类灵长类动物中的1型和疱疹 - 变化）。 最初，我们使用了 恒河猴检查疱疹病毒载体的渗透 脑内注射后（使用新颖的立体定向 微注射设备）和对该载体的宿主响应。 到 我们检查了两只动物的日期。 麻醉，放置在静脉乳液中，颅骨群 在无菌条件下进行。 使用微注射设备 插入了四个26 26量规针，彼此相距5毫米 10毫米进入右额叶皮层。 疱疹病毒（总共1 x 109 在120分钟内注入100 UL/注射的PFU。 后 去除注射，针和立体定向装置，然后 颅骨切开术通过常规手术程序封闭。 一 动物被安乐死并在注射后48小时检查和14小时 注：几天。 两只动物都有完整的验尸 考试。 两种动物在现场都有局部广泛的马拉西亚 注射。 在炎性细胞和 暴露于48小时后，动物偶尔会发生神经元 HSV-1突变体，但在14岁的安乐死和检查的动物中没有 注射后几天。 我们的初步研究表明，天真 可以感染的 HSV-1并安装对HSV-1的抗体响应，但不发展 广义。 尽管恒河猴是适合的模型 某些HSV-1研究，以充分评估HSV-1的安全性 人类中的突变体，我们目前正在使用猫头鹰猴（Aotus sp。）， 容易受到广义HSV-1感染的影响。 目前，两个猫头鹰 猴子已被HSV-1突变体（108 PFU）感染 在脑内（如上所述），并在 感染后四周和十二周。 既不病毒蛋白也不 在中枢神经系统和其他 检查的组织。 一年将调查其他动物 这三个提案。