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Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy
A safe and efficacious cancer medicine is necessary due to the increasing population of cancer patients whose particular diseases cannot be cured by the currently available treatment. Adenoviral (Ad) vectors represent a promising therapeutic medicine for human cancer therapy. However, several improv...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795172/ https://www.ncbi.nlm.nih.gov/pubmed/20046872 http://dx.doi.org/10.1371/journal.pone.0008526 |
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author | Tang, Yizhe Wu, Hongju Ugai, Hideyo Matthews, Qiana L. Curiel, David T. |
author_facet | Tang, Yizhe Wu, Hongju Ugai, Hideyo Matthews, Qiana L. Curiel, David T. |
author_sort | Tang, Yizhe |
collection | PubMed |
description | A safe and efficacious cancer medicine is necessary due to the increasing population of cancer patients whose particular diseases cannot be cured by the currently available treatment. Adenoviral (Ad) vectors represent a promising therapeutic medicine for human cancer therapy. However, several improvements are needed in order for Ad vectors to be effective cancer therapeutics, which include, but are not limited to, improvement of cellular uptake, enhanced cancer cell killing activity, and the capability of vector visualization and tracking once injected into the patients. To this end, we attempted to develop an Ad as a multifunctional platform incorporating targeting, imaging, and therapeutic motifs. In this study, we explored the utility of this proposed platform by generating an Ad vector containing the poly-lysine (pK), the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK), and the monomeric red fluorescent protein (mRFP1) as targeting, tumor cell killing, and imaging motifs, respectively. Our study herein demonstrates the generation of the triple mosaic Ad vector with pK, HSV-1 TK, and mRFP1 at the carboxyl termini of Ad minor capsid protein IX (pIX). In addition, the functionalities of pK, HSV-1 TK, and mRFP1 proteins on the Ad vector were retained as confirmed by corresponding functional assays, indicating the potential multifunctional application of this new Ad vector for cancer gene therapy. The validation of the triple mosaic Ad vectors also argues for the ability of pIX modification as a base for the development of multifunctional Ad vectors. |
format | Text |
id | pubmed-2795172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27951722009-12-31 Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy Tang, Yizhe Wu, Hongju Ugai, Hideyo Matthews, Qiana L. Curiel, David T. PLoS One Research Article A safe and efficacious cancer medicine is necessary due to the increasing population of cancer patients whose particular diseases cannot be cured by the currently available treatment. Adenoviral (Ad) vectors represent a promising therapeutic medicine for human cancer therapy. However, several improvements are needed in order for Ad vectors to be effective cancer therapeutics, which include, but are not limited to, improvement of cellular uptake, enhanced cancer cell killing activity, and the capability of vector visualization and tracking once injected into the patients. To this end, we attempted to develop an Ad as a multifunctional platform incorporating targeting, imaging, and therapeutic motifs. In this study, we explored the utility of this proposed platform by generating an Ad vector containing the poly-lysine (pK), the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK), and the monomeric red fluorescent protein (mRFP1) as targeting, tumor cell killing, and imaging motifs, respectively. Our study herein demonstrates the generation of the triple mosaic Ad vector with pK, HSV-1 TK, and mRFP1 at the carboxyl termini of Ad minor capsid protein IX (pIX). In addition, the functionalities of pK, HSV-1 TK, and mRFP1 proteins on the Ad vector were retained as confirmed by corresponding functional assays, indicating the potential multifunctional application of this new Ad vector for cancer gene therapy. The validation of the triple mosaic Ad vectors also argues for the ability of pIX modification as a base for the development of multifunctional Ad vectors. Public Library of Science 2009-12-31 /pmc/articles/PMC2795172/ /pubmed/20046872 http://dx.doi.org/10.1371/journal.pone.0008526 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Tang, Yizhe Wu, Hongju Ugai, Hideyo Matthews, Qiana L. Curiel, David T. Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy |
title | Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy |
title_full | Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy |
title_fullStr | Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy |
title_full_unstemmed | Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy |
title_short | Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy |
title_sort | derivation of a triple mosaic adenovirus for cancer gene therapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795172/ https://www.ncbi.nlm.nih.gov/pubmed/20046872 http://dx.doi.org/10.1371/journal.pone.0008526 |
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