The Establishment of Gene Therapy with and Gene Expression Regulation of Adenoviral Vector Serotype 35

35型腺病毒载体基因治疗的建立及基因表达调控

• 批准号: 21592242
• 负责人: MORI Keisuke
• 金额: $ 2.83万
• 依托单位: Saitama 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: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592242/
• 关键词: 眼細胞生物学; 遺伝子治療; アデノウイルスベクター; 血清型; 血管新生; 神経保護

Adenoviral vectors(Ad) have several attractive properties, including high transduction efficiency, transduction of a wide spectrum of dividing and non-dividing cells and absence of random integration into the host genome. Two phase I clinical trials using adenoviral vector have successfully been conducted in 2005 and 2006, one in a pediatric population, and the other in an elderly population. However, since Ad serotype 5 is highly prevalent in the human population, many individuals have been exposed to Ad5 and subsequently, have generated a dose-dependent neutralizing antibody response. This antibody response toAd5 is thought by many to contribute to a shorter duration of transgene expression, which is considered to be a disadvantage of adenoviral vector therapy. In this study we provided the evidence that Ad35 and Ad28 delivered subretinally gave prolonged gene expression as compared to conventional Ad5. These facts indicate the basis for the development of therapeutic protein agents that are applicable to the pathogenesis and treatment of ocular diseases such as age-related macular degeneration.

腺病毒载体（Ad）具有一些吸引人的特性，包括高转导效率、广泛的分裂和非分裂细胞转导以及不随机整合到宿主基因组中。2005年和2006年成功地进行了两项使用腺病毒载体的I期临床试验，一项是在儿科人群中，另一项是在老年人人群中。然而，由于Ad血清型5在人群中高度流行，许多个体暴露于Ad5并随后产生剂量依赖性中和抗体反应。许多人认为，这种针对ad5的抗体反应有助于缩短转基因表达的持续时间，这被认为是腺病毒载体治疗的一个缺点。在这项研究中，我们提供的证据表明，与传统的Ad5相比，视网膜下递送的Ad35和Ad28基因表达时间更长。这些事实为开发适用于诸如年龄相关性黄斑变性等眼部疾病的发病机制和治疗的治疗性蛋白制剂奠定了基础。

项目成果

Complement Factor H and High-Temperature Requirement A-1 Genotypes and Treatment Response of Age-related Macular Degeneration

• DOI: 10.1016/j.ophtha.2010.04.007
• 发表时间: 2011-01-01
• 期刊: OPHTHALMOLOGY
• 影响因子: 13.7
• 作者: Tsuchihashi, Takashi;Mori, Keisuke;Yoneya, Shin
• 通讯作者: Yoneya, Shin

Comparison of Transduction Efficiency and Intraocular Localization of Reporter Genes After Intravitreal and Subretinal Injection of the Adenovirus Vectors of Serotypes 5, 28, and 35 With Fiber Modifications

玻璃体内和视网膜下注射纤维修饰的血清型 5、28 和 35 腺病毒载体后报告基因的转导效率和眼内定位的比较

• 发表时间: 2010
• 作者: K. Ueyama;K. Mori;M. M. Hamilton;H. Omata;P. L. Gehlbach;L. L. Wei;S. Yoneya.
• 通讯作者: S. Yoneya.

Association of Elastin Gene Polymorphism to Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

• DOI: 10.1167/iovs.11-8205
• 发表时间: 2011-11-01
• 期刊: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
• 影响因子: 4.4
• 作者: Yamashiro, Kenji;Mori, Keisuke;Yoshimura, Nagahisa
• 通讯作者: Yoshimura, Nagahisa

加齢黄斑変性に対する新しい考え方

思考年龄相关性黄斑变性的新方法

• 发表时间: 2012
• 作者: Yamashiro K;Mori K;Nakata I;Tsuchihashi T;Horie-Inoue K;Nakanishi H;Tsujikawa A;Saito M;Iida T;Yamada R;Matsuda F;Inoue S;Awata T;Yoneya S;Yoshimura N;森圭介
• 通讯作者: 森圭介

インストラクションコース明日からの診療に役立つ基礎研究の最新トピックス

指导课程 对未来医疗有用的基础研究的最新主题

• 发表时间: 2010
• 作者: K.Ueyama;K.Mori;et al;Mori K;Keisuke Mori;森圭介
• 通讯作者: 森圭介