Introduction of tyrosine hydroxylase gene into the cells from brain for the treatment of parkinson's disease.

将酪氨酸羟化酶基因导入脑细胞以治疗帕金森病。

• 批准号: 11672264
• 负责人: KOYABU Noriko
• 金额: $ 1.92万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672264/
• 关键词: Gene Therapy; HVJ-liposomes; Parkinson' disease; Brain capillary endothelial cells; Blood-brain barrier; Glial-Derived Neurotrophic Factor; in vitro; in vivo; 遺伝子の発現

1. The hemagglutation virus of Japan (HVJ)-liposomes were found to be a useful tool for the efficient introduction of macromolecules, including oligodeoxynucleotide, into cultured brain capillary endothelial cells in vitro.2. Using HVJ-liposomes encapsulating a β-galactosidase gene expression vector, the gene was demonstrated to be efficiently transfered into cultured brain capillary endothelial cells in vitro.3. The efficient transfer of gene into brain capillary in vivo was achieved by the administration of the HVJ-liposomes encapsulating a β-galactosidase gene expression vector into carotid artery. The expression of β-galactosidase at brain capillaries was found throughout the parenchyma.4. The above results (2 and 3) indicate that the HVJ-liposome is a useful vector to transfer foreign gene into the brain capillary endothelium in vitro and in vivo.5. Additional study demonstrated that the cultured mouse brain endothelial cells transfected with mouse glial-derived neurotrophic factor (GDNF) cDNA was found to secrete mature GDNF predominantly to abluminal side (brain side).

1. 日本血凝病毒（HVJ）-脂质体被发现是将大分子（包括寡脱氧核苷酸）引入体外培养的脑毛细血管内皮细胞中的有用工具。2.使用HVJ-脂质体封装β-半乳糖苷酶基因表达。载体，证明该基因可有效转入体外培养的脑毛细血管内皮细胞。 3．通过将封装有β-半乳糖苷酶基因表达载体的HVJ-脂质体注射到颈动脉中，在体内的毛细血管中发现了β-半乳糖苷酶在整个脑实质中的表达。4．表明HVJ-脂质体是体外和体内将外源基因转移到脑毛细血管内皮的有用载体。5．转染小鼠胶质源性神经营养因子（GDNF）cDNA的小鼠脑内皮细胞被发现主要向近腔侧（脑侧）分泌成熟的GDNF。

项目成果

Hirotami Matsuo et al.: "Efficient introduction of macromolecules and oligonucleotide into brain capillary endothelial cells using HVJ-Liposomes."Journal of Drug Targeting. 8(4). 207-216 (2000)

Hirotami Matsuo 等人：“使用 HVJ 脂质体将大分子和寡核苷酸有效引入脑毛细血管内皮细胞。”药物靶向杂志。

H.Matsuo, et al.: "Efficient introduction of macromolecules and oligonucleotide into brain capillary endothelial cells using HVJ-Liposomes."Journal of Drug Targeting. 8 (4). 207-216 (2000)

H.Matsuo 等人：“使用 HVJ-脂质体将大分子和寡核苷酸有效引入脑毛细血管内皮细胞。”药物靶向杂志。

Hirotami Matsuo et al.: "Efficient introduction of macromolecules and oligonucleotides into brain capillary endotherial cells using HVJ-Liposomes."Journal of Drug Targeting. 8(4). 207-216 (2000)

Hirotami Matsuo 等人：“使用 HVJ 脂质体将大分子和寡核苷酸有效引入脑毛细血管内皮细胞。”药物靶向杂志。