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Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1

Investigations of anti-HIV-1 human hematopoietic stem/progenitor cell (HSPC)-based gene therapy have been performed by HIV-1 challenge after the engraftment of gene-modified HSPCs in humanized mouse models. However, the clinical application of gene therapy is to treat HIV-1-infected patients. Here,...

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Autores principales: Khamaikawin, Wannisa, Shimizu, Saki, Kamata, Masakazu, Cortado, Ruth, Jung, Yujin, Lam, Jennifer, Wen, Jing, Kim, Patrick, Xie, Yiming, Kim, Sanggu, Arokium, Hubert, Presson, Angela P., Chen, Irvin S.Y., An, Dong Sung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751878/
https://www.ncbi.nlm.nih.gov/pubmed/29322065
http://dx.doi.org/10.1016/j.omtm.2017.11.008
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author Khamaikawin, Wannisa
Shimizu, Saki
Kamata, Masakazu
Cortado, Ruth
Jung, Yujin
Lam, Jennifer
Wen, Jing
Kim, Patrick
Xie, Yiming
Kim, Sanggu
Arokium, Hubert
Presson, Angela P.
Chen, Irvin S.Y.
An, Dong Sung
author_facet Khamaikawin, Wannisa
Shimizu, Saki
Kamata, Masakazu
Cortado, Ruth
Jung, Yujin
Lam, Jennifer
Wen, Jing
Kim, Patrick
Xie, Yiming
Kim, Sanggu
Arokium, Hubert
Presson, Angela P.
Chen, Irvin S.Y.
An, Dong Sung
author_sort Khamaikawin, Wannisa
collection PubMed
description Investigations of anti-HIV-1 human hematopoietic stem/progenitor cell (HSPC)-based gene therapy have been performed by HIV-1 challenge after the engraftment of gene-modified HSPCs in humanized mouse models. However, the clinical application of gene therapy is to treat HIV-1-infected patients. Here, we developed a new method to investigate an anti-HIV-1 HSPC-based gene therapy in humanized mice previously infected with HIV-1. First, humanized mice were infected with HIV-1. When plasma viremia reached >10(7) copies/mL 3 weeks after HIV-1 infection, the mice were myeloablated with busulfan and transplanted with anti-HIV-1 gene-modified CD34(+) HSPCs transduced with a lentiviral vector expressing two short hairpin RNAs (shRNAs) against CCR5 and HIV-1 long terminal repeat (LTR), along with human thymus tissue under the kidney capsule. Anti-HIV-1 vector-modified human CD34(+) HSPCs successfully repopulated peripheral blood and lymphoid tissues in HIV-1 previously infected humanized mice. Anti-HIV-1 shRNA vector-modified CD4(+) T lymphocytes showed selective advantage in HIV-1 previously infected humanized mice. This new method will be useful for investigations of anti-HIV-1 gene therapy when testing in a more clinically relevant experimental setting.
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spelling pubmed-57518782018-01-10 Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1 Khamaikawin, Wannisa Shimizu, Saki Kamata, Masakazu Cortado, Ruth Jung, Yujin Lam, Jennifer Wen, Jing Kim, Patrick Xie, Yiming Kim, Sanggu Arokium, Hubert Presson, Angela P. Chen, Irvin S.Y. An, Dong Sung Mol Ther Methods Clin Dev Article Investigations of anti-HIV-1 human hematopoietic stem/progenitor cell (HSPC)-based gene therapy have been performed by HIV-1 challenge after the engraftment of gene-modified HSPCs in humanized mouse models. However, the clinical application of gene therapy is to treat HIV-1-infected patients. Here, we developed a new method to investigate an anti-HIV-1 HSPC-based gene therapy in humanized mice previously infected with HIV-1. First, humanized mice were infected with HIV-1. When plasma viremia reached >10(7) copies/mL 3 weeks after HIV-1 infection, the mice were myeloablated with busulfan and transplanted with anti-HIV-1 gene-modified CD34(+) HSPCs transduced with a lentiviral vector expressing two short hairpin RNAs (shRNAs) against CCR5 and HIV-1 long terminal repeat (LTR), along with human thymus tissue under the kidney capsule. Anti-HIV-1 vector-modified human CD34(+) HSPCs successfully repopulated peripheral blood and lymphoid tissues in HIV-1 previously infected humanized mice. Anti-HIV-1 shRNA vector-modified CD4(+) T lymphocytes showed selective advantage in HIV-1 previously infected humanized mice. This new method will be useful for investigations of anti-HIV-1 gene therapy when testing in a more clinically relevant experimental setting. American Society of Gene & Cell Therapy 2017-12-01 /pmc/articles/PMC5751878/ /pubmed/29322065 http://dx.doi.org/10.1016/j.omtm.2017.11.008 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Khamaikawin, Wannisa
Shimizu, Saki
Kamata, Masakazu
Cortado, Ruth
Jung, Yujin
Lam, Jennifer
Wen, Jing
Kim, Patrick
Xie, Yiming
Kim, Sanggu
Arokium, Hubert
Presson, Angela P.
Chen, Irvin S.Y.
An, Dong Sung
Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1
title Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1
title_full Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1
title_fullStr Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1
title_full_unstemmed Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1
title_short Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected with HIV-1
title_sort modeling anti-hiv-1 hspc-based gene therapy in humanized mice previously infected with hiv-1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751878/
https://www.ncbi.nlm.nih.gov/pubmed/29322065
http://dx.doi.org/10.1016/j.omtm.2017.11.008
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