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Efficient gene transfer into T lymphocytes by fiber-modified human adenovirus 5
BACKGROUND: The gene transduction efficiency of adenovirus to hematopoietic cells, especially T lymphocytes, is needed to be improved. The purpose of this study is to improve the transduction efficiency of T lymphocytes by using fiber-modified human adenovirus 5 (HAdV-5) vectors. RESULTS: Four fiber...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480437/ https://www.ncbi.nlm.nih.gov/pubmed/31014302 http://dx.doi.org/10.1186/s12896-019-0514-x |
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author | Lv, Yun Xiao, Feng-Jun Wang, Yi Zou, Xiao-Hui Wang, Hua Wang, Hai-Yan Wang, Li-Sheng Lu, Zhuo-Zhuang |
author_facet | Lv, Yun Xiao, Feng-Jun Wang, Yi Zou, Xiao-Hui Wang, Hua Wang, Hai-Yan Wang, Li-Sheng Lu, Zhuo-Zhuang |
author_sort | Lv, Yun |
collection | PubMed |
description | BACKGROUND: The gene transduction efficiency of adenovirus to hematopoietic cells, especially T lymphocytes, is needed to be improved. The purpose of this study is to improve the transduction efficiency of T lymphocytes by using fiber-modified human adenovirus 5 (HAdV-5) vectors. RESULTS: Four fiber-modified human adenovirus 5 (HAdV-5) vectors were investigated to transduce hematopoietic cells. F35-EG or F11p-EG were HAdV-35 or HAdV-11p fiber pseudotyped HAdV-5, and HR-EG or CR-EG vectors were generated by incorporating RGD motif to the HI loop or to the C-terminus of F11p-EG fiber. All vectors could transduce more than 90% of K562 or Jurkat cells at an multiplicity of infection (MOI) of 500 viral particle per cell (vp/cell). All vectors except HR-EG could transduce nearly 90% cord blood CD34+ cells or 80% primary human T cells at the MOI of 1000, and F11p-EG showed slight superiority to F35-EG and CR-EG. Adenoviral vectors transduced CD4+ T cells a little more efficiently than they did to CD8+ T cells. These vectors showed no cytotoxicity at an MOI as high as 1000 vp/cell because the infected and uninfected T cells retained the same CD4/CD8 ratio and cell growth rate. CONCLUSIONS: HAdV-11p fiber pseudotyped HAdV-5 could effectively transduce human T cells when human EF1a promoter was used to control the expression of transgene, suggesting its possible application in T cell immunocellular therapy. |
format | Online Article Text |
id | pubmed-6480437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64804372019-05-01 Efficient gene transfer into T lymphocytes by fiber-modified human adenovirus 5 Lv, Yun Xiao, Feng-Jun Wang, Yi Zou, Xiao-Hui Wang, Hua Wang, Hai-Yan Wang, Li-Sheng Lu, Zhuo-Zhuang BMC Biotechnol Research Article BACKGROUND: The gene transduction efficiency of adenovirus to hematopoietic cells, especially T lymphocytes, is needed to be improved. The purpose of this study is to improve the transduction efficiency of T lymphocytes by using fiber-modified human adenovirus 5 (HAdV-5) vectors. RESULTS: Four fiber-modified human adenovirus 5 (HAdV-5) vectors were investigated to transduce hematopoietic cells. F35-EG or F11p-EG were HAdV-35 or HAdV-11p fiber pseudotyped HAdV-5, and HR-EG or CR-EG vectors were generated by incorporating RGD motif to the HI loop or to the C-terminus of F11p-EG fiber. All vectors could transduce more than 90% of K562 or Jurkat cells at an multiplicity of infection (MOI) of 500 viral particle per cell (vp/cell). All vectors except HR-EG could transduce nearly 90% cord blood CD34+ cells or 80% primary human T cells at the MOI of 1000, and F11p-EG showed slight superiority to F35-EG and CR-EG. Adenoviral vectors transduced CD4+ T cells a little more efficiently than they did to CD8+ T cells. These vectors showed no cytotoxicity at an MOI as high as 1000 vp/cell because the infected and uninfected T cells retained the same CD4/CD8 ratio and cell growth rate. CONCLUSIONS: HAdV-11p fiber pseudotyped HAdV-5 could effectively transduce human T cells when human EF1a promoter was used to control the expression of transgene, suggesting its possible application in T cell immunocellular therapy. BioMed Central 2019-04-24 /pmc/articles/PMC6480437/ /pubmed/31014302 http://dx.doi.org/10.1186/s12896-019-0514-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Lv, Yun Xiao, Feng-Jun Wang, Yi Zou, Xiao-Hui Wang, Hua Wang, Hai-Yan Wang, Li-Sheng Lu, Zhuo-Zhuang Efficient gene transfer into T lymphocytes by fiber-modified human adenovirus 5 |
title | Efficient gene transfer into T lymphocytes by fiber-modified human adenovirus 5 |
title_full | Efficient gene transfer into T lymphocytes by fiber-modified human adenovirus 5 |
title_fullStr | Efficient gene transfer into T lymphocytes by fiber-modified human adenovirus 5 |
title_full_unstemmed | Efficient gene transfer into T lymphocytes by fiber-modified human adenovirus 5 |
title_short | Efficient gene transfer into T lymphocytes by fiber-modified human adenovirus 5 |
title_sort | efficient gene transfer into t lymphocytes by fiber-modified human adenovirus 5 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480437/ https://www.ncbi.nlm.nih.gov/pubmed/31014302 http://dx.doi.org/10.1186/s12896-019-0514-x |
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