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Investigation of the peak action wavelength of light-activated gene transduction (LAGT)

Light-activated gene transduction (LAGT) is an approach to localize gene therapy via preactivation of cells with UV light, which facilitates transduction by recombinant adeno-associated virus vectors. Prior studies demonstrated that UVC induces LAGT secondary to pyrimidine dimer formation, while UVA...

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Autores principales: Myakishev-Rempel, Max, Kuper, Jerry, Mintz, Benjamin, Hutchinson, Sara, Voris, Jay, Zavislan, Katrina, Offley, Sarah, Nardia, Frances Barg, Yaseen, Zaneb, Yen, Tony, Zavislan, James, Maloney, Michael D., Schwarz, Edward M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530381/
https://www.ncbi.nlm.nih.gov/pubmed/21490685
http://dx.doi.org/10.1038/gt.2011.47
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author Myakishev-Rempel, Max
Kuper, Jerry
Mintz, Benjamin
Hutchinson, Sara
Voris, Jay
Zavislan, Katrina
Offley, Sarah
Nardia, Frances Barg
Yaseen, Zaneb
Yen, Tony
Zavislan, James
Maloney, Michael D.
Schwarz, Edward M.
author_facet Myakishev-Rempel, Max
Kuper, Jerry
Mintz, Benjamin
Hutchinson, Sara
Voris, Jay
Zavislan, Katrina
Offley, Sarah
Nardia, Frances Barg
Yaseen, Zaneb
Yen, Tony
Zavislan, James
Maloney, Michael D.
Schwarz, Edward M.
author_sort Myakishev-Rempel, Max
collection PubMed
description Light-activated gene transduction (LAGT) is an approach to localize gene therapy via preactivation of cells with UV light, which facilitates transduction by recombinant adeno-associated virus vectors. Prior studies demonstrated that UVC induces LAGT secondary to pyrimidine dimer formation, while UVA induces LAGT secondary to reactive oxygen species (ROS) generation. However, the empirical UVB boundary of these UV effects is unknown. Thus, we aimed to define the action spectra for UV-induced LAGT independent of DNA damage, and determine an optimal wavelength to maximize safety and efficacy. Results: UV at 288, 311 and 320nm produced significant dose-dependent LAGT effects, of which the maximum (800-fold) was observed with 4kJ/m(2) at 311nm. Consistent with its robust cytotoxicity, 288nm produced significantly high levels of DNA damage at all doses tested, while 311, 320 and 330nm did not generate pyrimidine dimers and produced low levels of DNA damage detected by comet assay. While 288nm failed to induce ROS, the other wavelengths were effective, with the maximum (10-fold) effect observed with 30 kJ/m(2) at 311nm. An in vivo pilot study assessing 311nm-induced LAGT of rabbit articular chondrocytes demonstrated a significant 6.6-fold (p<0.05) increase in transduction with insignificant cytotoxicity. Conclusion: 311nm was found to be the optimal wavelength for LAGT based on its superior efficacy at the peak dose, and its broad safety range that is remarkably wider than the other UV wavelengths tested.
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spelling pubmed-35303812012-12-26 Investigation of the peak action wavelength of light-activated gene transduction (LAGT) Myakishev-Rempel, Max Kuper, Jerry Mintz, Benjamin Hutchinson, Sara Voris, Jay Zavislan, Katrina Offley, Sarah Nardia, Frances Barg Yaseen, Zaneb Yen, Tony Zavislan, James Maloney, Michael D. Schwarz, Edward M. Gene Ther Article Light-activated gene transduction (LAGT) is an approach to localize gene therapy via preactivation of cells with UV light, which facilitates transduction by recombinant adeno-associated virus vectors. Prior studies demonstrated that UVC induces LAGT secondary to pyrimidine dimer formation, while UVA induces LAGT secondary to reactive oxygen species (ROS) generation. However, the empirical UVB boundary of these UV effects is unknown. Thus, we aimed to define the action spectra for UV-induced LAGT independent of DNA damage, and determine an optimal wavelength to maximize safety and efficacy. Results: UV at 288, 311 and 320nm produced significant dose-dependent LAGT effects, of which the maximum (800-fold) was observed with 4kJ/m(2) at 311nm. Consistent with its robust cytotoxicity, 288nm produced significantly high levels of DNA damage at all doses tested, while 311, 320 and 330nm did not generate pyrimidine dimers and produced low levels of DNA damage detected by comet assay. While 288nm failed to induce ROS, the other wavelengths were effective, with the maximum (10-fold) effect observed with 30 kJ/m(2) at 311nm. An in vivo pilot study assessing 311nm-induced LAGT of rabbit articular chondrocytes demonstrated a significant 6.6-fold (p<0.05) increase in transduction with insignificant cytotoxicity. Conclusion: 311nm was found to be the optimal wavelength for LAGT based on its superior efficacy at the peak dose, and its broad safety range that is remarkably wider than the other UV wavelengths tested. 2011-04-14 2011-11 /pmc/articles/PMC3530381/ /pubmed/21490685 http://dx.doi.org/10.1038/gt.2011.47 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Myakishev-Rempel, Max
Kuper, Jerry
Mintz, Benjamin
Hutchinson, Sara
Voris, Jay
Zavislan, Katrina
Offley, Sarah
Nardia, Frances Barg
Yaseen, Zaneb
Yen, Tony
Zavislan, James
Maloney, Michael D.
Schwarz, Edward M.
Investigation of the peak action wavelength of light-activated gene transduction (LAGT)
title Investigation of the peak action wavelength of light-activated gene transduction (LAGT)
title_full Investigation of the peak action wavelength of light-activated gene transduction (LAGT)
title_fullStr Investigation of the peak action wavelength of light-activated gene transduction (LAGT)
title_full_unstemmed Investigation of the peak action wavelength of light-activated gene transduction (LAGT)
title_short Investigation of the peak action wavelength of light-activated gene transduction (LAGT)
title_sort investigation of the peak action wavelength of light-activated gene transduction (lagt)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530381/
https://www.ncbi.nlm.nih.gov/pubmed/21490685
http://dx.doi.org/10.1038/gt.2011.47
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