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

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.

我们研究了利用腺相关病毒（AAV）载体对异色性脑白质营养不良（MLD）和低磷酸症（HPP）模型小鼠进行产前/新生儿基因治疗的可行性。将AAV载体静脉注射入新生MLD小鼠后，检测到基因通过血脑屏障进入大脑的全局转移和长期基因表达，无免疫反应。治疗后神经症状明显改善。HPP小鼠胎儿经腹腔注射AAV载体。活产小鼠表现出矿化改善、表型纠正和生存时间延长。这些数据表明，围产期全身注射AAV载体是治疗MLD和HPP等严重遗传性疾病的有效策略。

项目成果

Rescue of Severe Infantile Hypophosphatasia Mice by AAV-Mediated Sustained Expression of Soluble Alkaline Phosphatase

• DOI: 10.1089/hum.2010.210
• 发表时间: 2011-11-01
• 期刊: HUMAN GENE THERAPY
• 影响因子: 4.2
• 作者: Matsumoto, Tae;Miyake, Koichi;Shimada, Takashi
• 通讯作者: Shimada, Takashi

Gene therapy for lethalmurine hyopophosphatasia.

致死鼠低磷酸酯酶症的基因治疗。

• 发表时间: 2012
• 作者: Dai X;Shirakata T;Tohyama M;Hanakawa Y;Okazaki H;and Sayama K.;Shimada T
• 通讯作者: Shimada T

Development of adeno-associated viral (AAV) vectormediated muscle directed systemic anti-angiogenic cancer gene therapy.

腺相关病毒（AAV）载体介导的肌肉定向系统性抗血管生成癌症基因疗法的开发。

• 发表时间: 2010
• 作者: Shimmura C;Suda S;Tsuchiya KJ;Hashimoto K;Ohno K;Matsuzaki H;Iwata K;Matsumoto K;Wakuda T;Kameno Y;Suzuki K;Tsujii M;Nakamura K;Takei N;Mori N;Miyake K
• 通讯作者: Miyake K

Global gene transfer in the CNS and phenotypic correction of MLD model mice by systemic neonatal injection of serotype 9 AAV vector.

通过新生儿全身注射血清型 9 AAV 载体进行中枢神经系统的整体基因转移和 MLD 模型小鼠的表型校正。

• 发表时间: 2010
• 作者: Miyake N;Miyake K;Asakawa N;Okabe M;Yamamoto M;Shimada T.
• 通讯作者: Shimada T.

Development and application of HIVvectors pseudotyped with HIV envelopes.

HIV包膜假型HIV载体的开发和应用。

• 发表时间: 2011
• 作者: Miyake;K.;Shimada;T.
• 通讯作者: T.