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j.omtn.2018.07.017.pdf | 1.78 MB | Adobe PDF | 見る/開く |
タイトル: | Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA |
著者: | Higaki, Kei Hirao, Masako Kawana-Tachikawa, Ai Iriguchi, Shoichi Kumagai, Ayako Ueda, Norihiro Wang, Bo Kamibayashi, Sanae Watanabe, Akira Nakauchi, Hiromitsu Suzuki, Kazuo Kaneko, Shin |
著者名の別形: | 檜垣, 慧 平尾, 理子 立川, 愛 入口, 翔一 熊谷, 綾子 上田, 格弘 王, 博 上林, 早苗 渡辺, 亮 中内, 啓光 鈴木, 一雄 金子, 新 |
キーワード: | HIV-1 induced pluripotent stem cells transcriptional-gene-silencing siRNA NF-κB macrophage |
発行日: | 7-Sep-2018 |
出版者: | Elsevier BV |
誌名: | Molecular Therapy - Nucleic Acids |
巻: | 12 |
開始ページ: | 793 |
終了ページ: | 804 |
抄録: | Highly active antiretroviral therapy (HAART) has markedly prolonged the prognosis of HIV-1 patients. However, lifelong dependency on HAART is a continuing challenge, and an effective therapeutic is much desired. Recently, introduction of short hairpin RNA (shRNA) targeting the HIV-1 promoter was found to suppress HIV-1 replication via transcriptional gene silencing (TGS). The technology is expected to be applied with hemato-lymphopoietic cell transplantation of HIV patients to suppress HIV transcription in transplanted hemato-lymphopoietic cells. Combination of the TGS technology with new cell transplantation strategy with induced pluripotent stem cell (iPSC)-derived hemato-lymphopoietic cells might contribute to new gene therapy in the HIV field. In this study, we evaluated iPSC-derived macrophage functions and feasibility of TGS technology in macrophages. Human iPSCs were transduced with shRNAs targeting the HIV-1 promoter region (shPromA) by using a lentiviral vector. The shPromA-transfected iPSCs were successfully differentiated into functional macrophages, and they exhibited strong protection against HIV-1 replication with alteration in the histone structure of the HIV-1 promoter region to induce heterochromatin formation. These results indicated that iPS-derived macrophage is a useful tool to investigate HIV infection and protection, and that the TGS technology targeting the HIV promoter is a potential candidate of new gene therapy. |
著作権等: | © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
URI: | http://hdl.handle.net/2433/242854 |
DOI(出版社版): | 10.1016/j.omtn.2018.07.017 |
PubMed ID: | 30141412 |
出現コレクション: | 学術雑誌掲載論文等 |
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