2. Academic Validation
  3. DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis

DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis

  • Nat Commun. 2017 Feb 6:8:14252. doi: 10.1038/ncomms14252.
Nirit Mor-Vaknin 1,  Anjan Saha 1 2,  Maureen Legendre 1,  Carmelo Carmona-Rivera 3,  M Asif Amin 4,  Bradley J Rabquer 4,  Marta J Gonzales-Hernandez 1,  Julie Jorns 5,  Smriti Mohan 6,  Srilakshmi Yalavarthi 4,  Dave A Pai 7,  Kristine Angevine 7,  Shelley J Almburg 8,  Jason S Knight 4,  Barbara S Adams 1,  Alisa E Koch 4 9,  David A Fox 4,  David R Engelke 7,  Mariana J Kaplan 3,  David M Markovitz 1 10
Affiliations

Affiliations

  • 1 Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • 2 Program in Cancer Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • 3 Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892, USA.
  • 4 Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • 5 Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • 6 Department of Pediatrics and Communicable Diseases, Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • 7 Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • 8 Microscopy &Image - Analysis Laboratory, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • 9 VA Medical Service, Department of Internal Medicine/Division of Rheumatology, University of Michigan, Ann Arbor, Michigan 48105, USA.
  • 10 Programs in Immunology, Cellular &Molecular Biology, and Cancer Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
PMID: 28165452 DOI: 10.1038/ncomms14252
Abstract

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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