• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文OA文献 >Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates
【2h】

Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates

机译：自我补充AAV载体外周静脉输注后肝的安全有效转导可在非人灵长类动物中稳定地表达人FIX

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The safety and efficacy of peripheral venous administration of a self-complementary adeno-associated viral vector encoding the human FIX gene (scAAV-LP1-hFIXco) was evaluated in nonhuman primates for gene therapy of hemophilia B. Peripheral vein infusion of 1 × 1012 vg/kg scAAV-LP1-hFIXco pseudotyped with serotype 8 capsid, in 3 macaques, resulted in stable therapeutic expression (more than 9 months) of human FIX (hFIX) at levels (1.1 ± 0.5 μg/mL, or 22% of normal) that were comparable to those achieved after direct delivery of the same vector dose into the portal circulation (1.3 ± 0.3 μg/mL, or 26% of normal). Importantly, the pattern of vector biodistribution after systemic and portal vein administration of scAAV-LP1-hFIXco was almost identical. Additionally, comparable levels of gene transfer were achieved in macaques with preexisting immunity to AAV8 following peripheral vein administration of 1 × 1012 vg/kg AAV5-pseudotyped scAAV-LP1-hFIXco. This confirms that alternative serotypes can circumvent preexisting naturally acquired immunity to AAV. Thus, peripheral venous administration of AAV5 and AAV8 vectors is safe and as effective at transducing the liver in nonhuman primates as direct vector administration into the portal circulation. These results should make vector administration to patients, especially those with a severe bleeding diathesis, significantly easier and safer.
机译：在非人灵长类动物中评估外周血静脉注射编码人FIX基因的自互补腺相关病毒载体（scAAV-LP1-hFIXco）的安全性和有效性，以进行血友病B基因治疗。外周静脉输注1×1012 vg / kg scAAV-LP1-hFIXco在8只猕猴中用血清型8衣壳进行假型化，导致人FIX（hFIX）的稳定治疗表达（超过9个月），水平为（1.1±0.5μg/ mL，或正常水平的22％）与将相同载体剂量直接递送至门脉循环后获得的结果相当（1.3±0.3μg/ mL，或正常值的26％）。重要的是，scAAV-LP1-hFIXco全身和门静脉给药后载体生物分布方式几乎相同。此外，在以1×1012 vg / kg AAV5-假型scAAV-LP1-hFIXco给予外周静脉后，在对AAV8既有免疫力的猕猴中，可获得相当水平的基因转移。这证实了其他血清型可以规避天然存在的对AAV的免疫力。因此，AAV5和AAV8载体的外周静脉给药是安全的，并且与直接载体给药进入门脉循环一样有效地在非人灵长类动物中转导肝脏。这些结果应该使向患者，尤其是那些具有严重出血素质的患者的载体给药明显更容易和更安全。

著录项

相似文献

  • 外文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号