Perinatal gene therapy for severe genetic diseases

严重遗传病的围产期基因治疗

• 批准号: 22390212
• 负责人: SHIMADA Takashi
• 金额: $ 12.15万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390212/
• 关键词: 遺伝子; 遺伝子治療; 遺伝病; 遺伝子; 遺伝子治療; 遺伝病

We investigated the feasibility of prenatal/neonatal gene therapy of both metachromatic leukodystrophy (MLD) and hypophosphatasia (HPP) model mice using adeno-associated viral (AAV) vectors. After intravenous injection of AAV vector into neonatal MLD mice, global gene transfer into the brain across the BBB and long term gene expression without immune reaction were detected. Significant improvement of neurological symptoms was observed after treatment. The fetuses of HPP mice underwent transuterine intraperitoneal injection of AAV vector. Live-born mice showed improved mineralization, phenotypic correction and prolonged survival. These data demonstrated that systemic injection of AAV vector in the perinatal period is an effective strategy for the treatment of severe genetic diseases such as MLD and HPP.

我们使用腺相关病毒（AAV）载体研究了正常白细胞营养不良（MLD）和下磷酸（HPP）模型小鼠的产前/新生儿基因治疗的可行性。在静脉注射AAV载体到新生儿MLD小鼠中后，全局基因转移到BBB的大脑中，并检测到长期基因表达没有免疫反应。治疗后观察到神经系统症状的显着改善。 HPP小鼠的胎儿接受了AAV载体的腹膜腹膜内注射。活出生的小鼠表现出改善的矿化，表型矫正和长时间的存活率。这些数据表明，在围产期内，全身注射AAV载体是治疗严重遗传疾病（如MLD和HPP）的有效策略。