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Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA
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 fou...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111070/ https://www.ncbi.nlm.nih.gov/pubmed/30141412 http://dx.doi.org/10.1016/j.omtn.2018.07.017 |
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author | Higaki, Kei Hirao, Masako Kawana-Tachikawa, Ai Iriguchi, Shoichi Kumagai, Ayako Ueda, Norihiro Bo, Wang Kamibayashi, Sanae Watanabe, Akira Nakauchi, Hiromitsu Suzuki, Kazuo Kaneko, Shin |
author_facet | Higaki, Kei Hirao, Masako Kawana-Tachikawa, Ai Iriguchi, Shoichi Kumagai, Ayako Ueda, Norihiro Bo, Wang Kamibayashi, Sanae Watanabe, Akira Nakauchi, Hiromitsu Suzuki, Kazuo Kaneko, Shin |
author_sort | Higaki, Kei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6111070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-61110702018-08-28 Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA Higaki, Kei Hirao, Masako Kawana-Tachikawa, Ai Iriguchi, Shoichi Kumagai, Ayako Ueda, Norihiro Bo, Wang Kamibayashi, Sanae Watanabe, Akira Nakauchi, Hiromitsu Suzuki, Kazuo Kaneko, Shin Mol Ther Nucleic Acids Article 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. American Society of Gene & Cell Therapy 2018-08-04 /pmc/articles/PMC6111070/ /pubmed/30141412 http://dx.doi.org/10.1016/j.omtn.2018.07.017 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Higaki, Kei Hirao, Masako Kawana-Tachikawa, Ai Iriguchi, Shoichi Kumagai, Ayako Ueda, Norihiro Bo, Wang Kamibayashi, Sanae Watanabe, Akira Nakauchi, Hiromitsu Suzuki, Kazuo Kaneko, Shin Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA |
title | Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA |
title_full | Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA |
title_fullStr | Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA |
title_full_unstemmed | Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA |
title_short | Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA |
title_sort | generation of hiv-resistant macrophages from ipscs by using transcriptional gene silencing and promoter-targeted rna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111070/ https://www.ncbi.nlm.nih.gov/pubmed/30141412 http://dx.doi.org/10.1016/j.omtn.2018.07.017 |
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