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DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis

Novel therapeutics are required for improving the management of chronic inflammatory diseases. Aptamers are single-stranded RNA or DNA molecules that have recently shown utility in a clinical setting, as they can specifically neutralize biomedically relevant proteins, particularly cell surface and e...

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Autores principales: Mor-Vaknin, Nirit, Saha, Anjan, Legendre, Maureen, Carmona-Rivera, Carmelo, Amin, M Asif, Rabquer, Bradley J., Gonzales-Hernandez, Marta J., Jorns, Julie, Mohan, Smriti, Yalavarthi, Srilakshmi, Pai, Dave A., Angevine, Kristine, Almburg, Shelley J., Knight, Jason S., Adams, Barbara S., Koch, Alisa E., Fox, David A., Engelke, David R., Kaplan, Mariana J., Markovitz, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303823/
https://www.ncbi.nlm.nih.gov/pubmed/28165452
http://dx.doi.org/10.1038/ncomms14252
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author Mor-Vaknin, Nirit
Saha, Anjan
Legendre, Maureen
Carmona-Rivera, Carmelo
Amin, M Asif
Rabquer, Bradley J.
Gonzales-Hernandez, Marta J.
Jorns, Julie
Mohan, Smriti
Yalavarthi, Srilakshmi
Pai, Dave A.
Angevine, Kristine
Almburg, Shelley J.
Knight, Jason S.
Adams, Barbara S.
Koch, Alisa E.
Fox, David A.
Engelke, David R.
Kaplan, Mariana J.
Markovitz, David M.
author_facet Mor-Vaknin, Nirit
Saha, Anjan
Legendre, Maureen
Carmona-Rivera, Carmelo
Amin, M Asif
Rabquer, Bradley J.
Gonzales-Hernandez, Marta J.
Jorns, Julie
Mohan, Smriti
Yalavarthi, Srilakshmi
Pai, Dave A.
Angevine, Kristine
Almburg, Shelley J.
Knight, Jason S.
Adams, Barbara S.
Koch, Alisa E.
Fox, David A.
Engelke, David R.
Kaplan, Mariana J.
Markovitz, David M.
author_sort Mor-Vaknin, Nirit
collection PubMed
description Novel therapeutics are required for improving the management of chronic inflammatory diseases. Aptamers are single-stranded RNA or DNA molecules that have recently shown utility in a clinical setting, as they can specifically neutralize biomedically relevant proteins, particularly cell surface and extracellular proteins. The nuclear chromatin protein DEK is a secreted chemoattractant that is abundant in the synovia of patients with juvenile idiopathic arthritis (JIA). Here, we show that DEK is crucial to the development of arthritis in mouse models, thus making it an appropriate target for aptamer-based therapy. Genetic depletion of DEK or treatment with DEK-targeted aptamers significantly reduces joint inflammation in vivo and greatly impairs the ability of neutrophils to form neutrophil extracellular traps (NETs). DEK is detected in spontaneously forming NETs from JIA patient synovial neutrophils, and DEK-targeted aptamers reduce NET formation. DEK is thus key to joint inflammation, and anti-DEK aptamers hold promise for the treatment of JIA and other types of arthritis.
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spelling pubmed-53038232017-02-27 DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis Mor-Vaknin, Nirit Saha, Anjan Legendre, Maureen Carmona-Rivera, Carmelo Amin, M Asif Rabquer, Bradley J. Gonzales-Hernandez, Marta J. Jorns, Julie Mohan, Smriti Yalavarthi, Srilakshmi Pai, Dave A. Angevine, Kristine Almburg, Shelley J. Knight, Jason S. Adams, Barbara S. Koch, Alisa E. Fox, David A. Engelke, David R. Kaplan, Mariana J. Markovitz, David M. Nat Commun Article Novel therapeutics are required for improving the management of chronic inflammatory diseases. Aptamers are single-stranded RNA or DNA molecules that have recently shown utility in a clinical setting, as they can specifically neutralize biomedically relevant proteins, particularly cell surface and extracellular proteins. The nuclear chromatin protein DEK is a secreted chemoattractant that is abundant in the synovia of patients with juvenile idiopathic arthritis (JIA). Here, we show that DEK is crucial to the development of arthritis in mouse models, thus making it an appropriate target for aptamer-based therapy. Genetic depletion of DEK or treatment with DEK-targeted aptamers significantly reduces joint inflammation in vivo and greatly impairs the ability of neutrophils to form neutrophil extracellular traps (NETs). DEK is detected in spontaneously forming NETs from JIA patient synovial neutrophils, and DEK-targeted aptamers reduce NET formation. DEK is thus key to joint inflammation, and anti-DEK aptamers hold promise for the treatment of JIA and other types of arthritis. Nature Publishing Group 2017-02-06 /pmc/articles/PMC5303823/ /pubmed/28165452 http://dx.doi.org/10.1038/ncomms14252 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Mor-Vaknin, Nirit
Saha, Anjan
Legendre, Maureen
Carmona-Rivera, Carmelo
Amin, M Asif
Rabquer, Bradley J.
Gonzales-Hernandez, Marta J.
Jorns, Julie
Mohan, Smriti
Yalavarthi, Srilakshmi
Pai, Dave A.
Angevine, Kristine
Almburg, Shelley J.
Knight, Jason S.
Adams, Barbara S.
Koch, Alisa E.
Fox, David A.
Engelke, David R.
Kaplan, Mariana J.
Markovitz, David M.
DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis
title DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis
title_full DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis
title_fullStr DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis
title_full_unstemmed DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis
title_short DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis
title_sort dek-targeting dna aptamers as therapeutics for inflammatory arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303823/
https://www.ncbi.nlm.nih.gov/pubmed/28165452
http://dx.doi.org/10.1038/ncomms14252
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