Identification of the cell type specific region for retroviral vector integration

逆转录病毒载体整合的细胞类型特异性区域的鉴定

• 批准号: 23701099
• 负责人: YOSHINO kazuhisa
• 金额: $ 2.66万
• 依托单位: Shinshu University
• 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-23701099/
• 关键词: 遺伝子治療; レトロウイルスベクター; Ｘ連鎖重症複合免疫不全症; insertional mutagenesis; IL-2レセプターγ鎖

Retroviral vector integration near the LMO2 promotor is the most likely cause of leukemogenesis in the gene therapy trails. Here, we showed identification of a high incidence region (HIR) for retroviral vector integration, which we had originally identified in the LMO2 promotor region, near the promotor region of the CCND2 locus, suggesting that there is the HIR in the promotor region of various genes. To perform comprehensive analysis of HIR, next-generation sequencer was applied to examine the analysis condition for the HIR. Furthermore, using the next-generation sequencer, 600 candidates for proto-oncogene or the cell proliferation-related gene, which are targets for the vector integration on HIR, were identified.

在基因治疗中，LMO2启动子附近的逆转录病毒载体整合是最可能导致白血病发生的原因。在这里，我们发现了一个逆转录病毒载体整合的高发区（HIR），我们最初在LMO2启动子区域发现，靠近CCND2位点的启动子区域，这表明在各种基因的启动子区域都存在HIR。为了对HIR进行全面分析，采用新一代测序仪对HIR的分析条件进行检测。此外，利用下一代测序仪，确定了600个候选原癌基因或细胞增殖相关基因，这些基因是HIR载体整合的靶标。

项目成果

Hydrophobic amino acid cluster in the cytoplasmic tail of interleukin-2 receptor βchain acts as a sorting signal for lysosome

白细胞介素2受体β链胞质尾部的疏水性氨基酸簇充当溶酶体的分选信号

• 作者: 天野勇治;その他
• 通讯作者: その他

A hydrophobic amino acid cluster inserted into the C-terminus of a recycling cell surface receptor functions as an endosomal sorting signal

• DOI: 10.1016/j.bbrc.2013.10.019
• 发表时间: 2013-11-08
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Amano, Yuji;Yoshino, Kazuhisa;Takeshita, Toshikazu
• 通讯作者: Takeshita, Toshikazu

Hrs Recognizes a Hydrophobic Amino Acid Cluster in Cytokine Receptors during Ubiquitin-independent Endosomal Sorting

• DOI: 10.1074/jbc.m110.191924
• 发表时间: 2011-04-29
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Amano, Yuji;Yamashita, Yuki;Takeshita, Toshikazu
• 通讯作者: Takeshita, Toshikazu