gene therapy using siena technology

使用锡耶纳技术的基因治疗

• 批准号: 23792014
• 负责人: IGARASHI Tsutomu
• 金额: $ 2.66万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23792014/
• 关键词: 網膜; 遺伝子治療; AAVベクター; siRNA; VEGF; 脈絡膜新生血管; 血管新生; 眼科; 新生血管; 抑制; 遺伝子; ウィルスベクター

To assess the feasibility of a gene therapeutic approach to treating choroidal neovascularization (CNV), we generated an adeno-associated virus type 8 vector (AAV8) encoding a small interfering RNA (siRNA) targeting vascular endothelial growth factor (VEGF), and determined its ability to inhibit angiogenesis. We made AAV8/SmVEGF-2. We injected AAV8/SmVEGF-2 or control vector (AAV8/GFP) into the subretinal space in C57BL/6 mice. The eyes were removed for flat mount analysis of CNV surface area. Subretinal delivery of AAV8/SmVEGF-2 significantly diminished CNV at the laser lesions, as compared to AAV8/GFP Using ELISA, we found that VEGF levels were reduced by approximately half in AAV8/SmVEGF-2 treated eyes. These results suggest that siRNA-VEGF can be expressed across the retina and that long-term suppression of CNV is possible through the use of stable AAV-mediated siRNA-VEGF expression.

为了评估基因治疗方法治疗脉络膜新生血管（CNV）的可行性，我们产生了一个腺相关病毒8型载体（AAV 8）编码的小干扰RNA（siRNA）靶向血管内皮生长因子（VEGF），并确定其抑制血管生成的能力。我们制备了AAV 8/SmVEGF-2。 我们将AAV 8/SmVEGF-2或对照载体（AAV 8/GFP）注射到C57 BL/6小鼠的视网膜下腔中。摘除眼睛进行CNV表面积的平片分析。与AAV 8/GFP相比，AAV 8/SmVEGF-2的视网膜下递送显著减少了激光损伤处的CNV。使用ELISA，我们发现在AAV 8/SmVEGF-2治疗的眼睛中VEGF水平降低了大约一半。这些结果表明siRNA-VEGF可以在整个视网膜中表达，并且通过使用稳定的AAV介导的siRNA-VEGF表达可以长期抑制CNV。

项目成果

Bone Marrow Cell Based Enzyme Replacement Prolongs Survival and Improves Disease Phenotypes In a Mouse Model Of Lethal Hypophosphatasia

基于骨髓细胞的酶替代可延长致命性低磷酸酯酶症小鼠模型的存活并改善疾病表型

• 发表时间: 2013
• 作者: Iijima O;Miyake K;Nakamura A;Igarashi T;Kanokoda C;Watanabe A;Shimada T
• 通讯作者: Shimada T

A new mutation in RP1L1 gene in occult macular dystrophy patient associated with a depolarizing-pattern of focal macular ERG

隐匿性黄斑营养不良患者 RP1L1 基因的新突变与局灶性黄斑 ERG 去极化模式相关

• 发表时间: 2012
• 期刊: Molecular Vision
• 影响因子: 2.2
• 作者: Kabuto T;Takahashi H;Goto-Fukuura Y;Igarashi T;Akahori M;Kameya S;Iwata T;Mizota A;Yamaki K;Miyake Y;Takahashi H
• 通讯作者: Takahashi H

Mean hemoglobin levels in venous blood samples and prevalence of anemia in Japanese elementary and junior high school students

日本中小学生静脉血平均血红蛋白水平与贫血患病率

• 发表时间: 2012
• 期刊: Journal of Nippon Medical School
• 影响因子: 1
• 作者: Igarashi T;Itoh Y;Maeda M;Igarashi T;Fukunaga Y
• 通讯作者: Fukunaga Y

A case of juvenile Sjögren’s syndrome with interstitial nephritis.

青少年干燥综合征伴间质性肾炎一例。

• 发表时间: 2012
• 期刊: Journal of Nippon Medical School.
• 作者: Igarashi T;Itoh Y;Shimizu A;Igarashi T;Yoshizaki K;Fukunaga Y.
• 通讯作者: Fukunaga Y.

A new mutation in RP1L1 gene in occult macular dystrophy patient associated with a depolarizing-pattern of focal macular ERG.

隐匿性黄斑营养不良患者 RP1L1 基因的新突变与局灶性黄斑 ERG 去极化模式相关。

• 发表时间: 2012
• 期刊: Molecular Vision.
• 作者: Kabuto T;Takahashi H;Goto-Fukuura Y;Igarashi T;Akahori M;Kameya S;Iwata T;Mizota A;Yamaki K;Miyake Y;Takahashi H.
• 通讯作者: Takahashi H.