Extrahepatic tissue-targeted gene therapy for phenylketonuria

苯丙酮尿症的肝外组织靶向基因治疗

• 批准号: 20591230
• 负责人: KUME Akihiro
• 金额: $ 2.91万
• 依托单位: Jichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591230/
• 关键词: 小児代謝; 栄養学; 遺伝子治療; フェニルケトン尿症; 先天代謝異常; アデノ随伴ウイルス

The feasibility of muscle-directed gene transfer for the treatment of phenylketonuria (PKU) was investigated. Small-sized promoters were examined for high expression in the context of self-complementary adeno-associated virus (scAAV) vector. Intramuscular injection of a scAAV encoding phenylalanine hydroxylase (PAH) did not show a significant effect in a mouse model of PKU. Simultaneous injection of three scAAV vectors encoding PAH, GTP cyclohydrolase I and 6-pyruvoil tetrahydrobiopterine synthase resulted in a significant, still moderate decrease of blood phenylalanine in PKU mice.

研究了肌肉定向基因转移治疗苯丙酮尿症（PKU）的可行性。小尺寸启动子在自互补腺相关病毒（scAAV）载体中进行了高表达检测。肌内注射编码苯丙氨酸羟化酶（PAH）的scAAV对PKU小鼠模型没有显著影响。同时注射编码PAH、GTP环水解酶I和6-丙酮醇四氢生物碱合成酶的三种scAAV载体，可导致PKU小鼠血液中苯丙氨酸显著且仍中度降低。

项目成果

A Phase I Study of Aromatic L-Amino Acid Decarboxylase Gene Therapy for Parkinson's Disease

• DOI: 10.1038/mt.2010.135
• 发表时间: 2010-09-01
• 期刊: MOLECULAR THERAPY
• 影响因子: 12.4
• 作者: Muramatsu, Shin-ichi;Fujimoto, Ken-ichi;Nakano, Imaharu
• 通讯作者: Nakano, Imaharu

Kinetics and defect of integrin expression on human CD34+ cells during MLV-derived retroviral transduction with a recombinant fibronectin for stem cell gene therapy.

用于干细胞基因治疗的 MLV 衍生逆转录病毒转导重组纤连蛋白过程中人 CD34+ 细胞上整合素表达的动力学和缺陷。

• 发表时间: 2009
• 作者: Horiuchi Y;Onodera M;Miyagawa Y;Sato B;Onda K;Katagiri YU;Okita H;Okada M;Otsu M;Kume A;Okuyaka T;Fujimoto J;Kuratsuji T;Kiyokawa N
• 通讯作者: Kiyokawa N

Promoter selection for muscle-directed self-complementary AAV toward hemophilia B gene thearapy.

用于血友病 B 基因治疗的肌肉定向自我互补 AAV 的启动子选择。

• 发表时间: 2009
• 作者: Okada;T.;Ogura,M.;水上浩明;Kume,A.
• 通讯作者: Kume,A.

Complete retoration of in vivo oxidative capacity for phenylalanine in self-complementary AAV vector-treated phenylketonuria mice.

自我补充 AAV 载体治疗的苯丙酮尿​​症小鼠体内苯丙氨酸氧化能力的完全恢复。

• 发表时间: 2008
• 作者: Kume A.;et al
• 通讯作者: et al

Improvement of monoamine metabolism in phenylketonuria mousebrain treated with a self-complementary adeno-associated vector.

用自我互补的腺相关载体处理苯丙酮尿症小鼠脑中单胺代谢的改善。

• 发表时间: 2009
• 作者: Yagi;H.
• 通讯作者: H.