Antinucleic aid antibody gene therapy for rheumatoid Arthritis and adult T cell Leukemia

类风湿关节炎和成人T细胞白血病的抗核辅助抗体基因治疗

• 批准号: 12557044
• 负责人: SASAKI Takeshi
• 金额: $ 8.38万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557044/
• 关键词: Gene therapy; antinucleic acid antibody; retrovirus; adult T cell leukemia virus; レトロウィルス; 成人型T細胞; 人工単鎖抗体; VH,VL; ヒトT細胞白血病ウイルス; V遺伝子

1.Expression of antibody against DNARNA hybrid in the cells.We first obtained hybridoma producing monoclonal anti-DMA RNA hybrid antibody and prepared the fragments of VH and VL gene encoding the antibody. Both fragments were bound for the expression of ScFv antibodies and introduced into vectors for the expression in the cells.2. Efficacy of gene therapy using anti-ScFv expression system for prevention of tabacco mosaic virus (TMV) infection.Tabacco which was introduced with anti-DNARNA hybrid ScFv genes, expressed ScFv mRNA and showed marked resistance to TMV infection.3. Blocking experiment of human adult T cell leukemia virus (HTLV-1) infection by gene therapy using anti-ScFv expression system.We are establishing for evaluation of efficacy of ScFv strategy in order to block HTLV-1 infection in T cells.

1.在细胞中表达抗DNARNA杂交瘤抗体我们首次获得了产生抗DNARNA杂交瘤抗体的单克隆杂交瘤细胞，并制备了编码该抗体的VH和VL基因片段。将两个片段结合用于表达单链抗体，并将其导入载体用于在细胞中表达.抗ScFv基因表达系统对烟草花叶病毒（TMV）感染的基因治疗效果研究将抗DNARNA杂合ScFv基因导入烟草，获得了ScFv mRNA表达，并对TMV感染表现出明显的抗性.利用抗单链抗体表达系统进行人成人T细胞白血病病毒（HTLV-1）感染的基因治疗阻断实验，旨在建立评价抗单链抗体策略阻断HTLV-1感染T细胞的有效性。

项目成果

Y.Fu, T.Sasaki et al.: "Regulation of TNF-α promoter by human parvovirus B19 NS1 through activation Of AP-1 and AP-2"J. Virology.. (in press). (2002)

Y.Fu、T.Sasaki 等人：“人细小病毒 B19 NS1 通过 AP-1 和 AP-2 的激活调节 TNF-α 启动子”J. Virology（2002 年出版）。

S.Takahashi, T.Sasaki ほか: "Genetic structure and regulation of a novel human gene, Klo1"Biochem, Bioph, Acta.. 91600. 1-5 (2001)

S.Takahashi、T.Sasaki 等人：“新型人类基因 Klo1 的遗传结构和调控”Biochem、Bioph、Acta.. 91600. 1-5 (2001)

H.Harigae, R.Ichinohasama, I.Miura, J.Kameoka, K.Meguro, K.Miyamura, O.Sasaki, I.Ishikawa, S.Takahashi, M.Kaku, T.Sasaki: "Primary marginal zone lymphoma of the thymus accompanied by chromosomal anomaly, 46X,dup(X)(P11 P22)"Cancer Genetics cytogenetics..

H.Harigae、R.Ichinohasama、I.Miura、J.Kameoka、K.Meguro、K.Miyamura、O.Sasaki、I.Ishikawa、S.Takahashi、M.Kaku、T.Sasaki：“原发性边缘区淋巴瘤

O.Sasaki, K.Meguro, Y.Tohmiya, T.Funato, S.Shibahara, T.Sasaki: "Structural alteration of retionblastoma protein-interacting zinc finger gene, RIZ, in human leukemia"Tohoku.J.Exp.Med.. (in press). (2002)

O.Sasaki、K.Meguro、Y.Tohmiya、T.Funato、S.Shibahara、T.Sasaki：“人类白血病中视网膜母细胞瘤蛋白相互作用锌指基因 RIZ 的结构改变”Tohoku.J.Exp.Med。

M.Takahashi, T.Funato, Y.Suzuki, H.Fujii, K.Kumuraishi, M.Kaku, T.Sasaki: "Chemically modified Ribozyme Targeting TNF-α mRNA rugulates TNF-α and IL-6 Synthesis in Synovial Fibroblasts of Patients with Rheumatoid Arthritis"J. Clin. Immunol.. (in press). (2

M.Takahashi、T.Funato、Y.Suzuki、H.Fujii、K.Kumuraishi、M.Kaku、T.Sasaki：“靶向 TNF-α mRNA 的化学修饰核酶调节滑膜成纤维细胞中 TNF-α 和 IL-6 的合成类风湿性关节炎患者”J. Clin.Immunol..（印刷中）。（2