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Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells

Methods for customizing and improving virus vector tropism are limited. In this study, we introduce a microRNA (miRNA)-regulated molecular method to enhance vector transduction without genome alteration. Based on the importance of adenovirus (Ad) vectors for cancer and gene treatment, we exemplified...

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Autores principales: Gao, Jian, Zhang, Wenli, Mese, Kemal, Bunz, Oskar, Lu, Fengmin, Ehrhardt, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358217/
https://www.ncbi.nlm.nih.gov/pubmed/32695840
http://dx.doi.org/10.1016/j.omtm.2020.06.010
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author Gao, Jian
Zhang, Wenli
Mese, Kemal
Bunz, Oskar
Lu, Fengmin
Ehrhardt, Anja
author_facet Gao, Jian
Zhang, Wenli
Mese, Kemal
Bunz, Oskar
Lu, Fengmin
Ehrhardt, Anja
author_sort Gao, Jian
collection PubMed
description Methods for customizing and improving virus vector tropism are limited. In this study, we introduce a microRNA (miRNA)-regulated molecular method to enhance vector transduction without genome alteration. Based on the importance of adenovirus (Ad) vectors for cancer and gene treatment, we exemplified this technology for an Ad type 5 (Ad5) vector temporally carrying a knob from Ad37. We constructed a producer cell line stably expressing a fused Ad5/37 chimeric fiber comprising the Ad5 shaft-tail and the Ad37 knob and a miRNA inhibiting Ad5 knob expression (HEK293-Ad5/37-miRNA). The chimeric Ad5/37 vector resulted in enhanced transduction rates in Ad37 adequately and Ad5 poorly transduced cells. Particularly, encapsidation of the oncolytic Ad5-human telomerase reverse transcriptase (hTERT) vector genome into the chimeric Ad5/37 capsid showed efficient transduction of NK-92 carrier cells. These infected carrier cells then delivered the oncolytic vector to tumor cells, which resulted in enhanced Ad5-hTERT-mediated tumor cell killing. We show that this transiently capsid-modified chimeric vector carrying an Ad5 genome displayed higher transduction efficiencies of natural killer cell-derived NK-92 cells utilized as carriers in cancer immune therapy. In summary, transiently modified adenoviral vectors will have important implications for cancer and gene therapy.
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spelling pubmed-73582172020-07-20 Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells Gao, Jian Zhang, Wenli Mese, Kemal Bunz, Oskar Lu, Fengmin Ehrhardt, Anja Mol Ther Methods Clin Dev Article Methods for customizing and improving virus vector tropism are limited. In this study, we introduce a microRNA (miRNA)-regulated molecular method to enhance vector transduction without genome alteration. Based on the importance of adenovirus (Ad) vectors for cancer and gene treatment, we exemplified this technology for an Ad type 5 (Ad5) vector temporally carrying a knob from Ad37. We constructed a producer cell line stably expressing a fused Ad5/37 chimeric fiber comprising the Ad5 shaft-tail and the Ad37 knob and a miRNA inhibiting Ad5 knob expression (HEK293-Ad5/37-miRNA). The chimeric Ad5/37 vector resulted in enhanced transduction rates in Ad37 adequately and Ad5 poorly transduced cells. Particularly, encapsidation of the oncolytic Ad5-human telomerase reverse transcriptase (hTERT) vector genome into the chimeric Ad5/37 capsid showed efficient transduction of NK-92 carrier cells. These infected carrier cells then delivered the oncolytic vector to tumor cells, which resulted in enhanced Ad5-hTERT-mediated tumor cell killing. We show that this transiently capsid-modified chimeric vector carrying an Ad5 genome displayed higher transduction efficiencies of natural killer cell-derived NK-92 cells utilized as carriers in cancer immune therapy. In summary, transiently modified adenoviral vectors will have important implications for cancer and gene therapy. American Society of Gene & Cell Therapy 2020-06-18 /pmc/articles/PMC7358217/ /pubmed/32695840 http://dx.doi.org/10.1016/j.omtm.2020.06.010 Text en © 2020 The Author(s) 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
Gao, Jian
Zhang, Wenli
Mese, Kemal
Bunz, Oskar
Lu, Fengmin
Ehrhardt, Anja
Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells
title Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells
title_full Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells
title_fullStr Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells
title_full_unstemmed Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells
title_short Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells
title_sort transient chimeric ad5/37 fiber enhances nk-92 carrier cell-mediated delivery of oncolytic adenovirus type 5 to tumor cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358217/
https://www.ncbi.nlm.nih.gov/pubmed/32695840
http://dx.doi.org/10.1016/j.omtm.2020.06.010
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