DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis. Nat Commun 2017 Feb 06;8:14252
Date
02/07/2017Pubmed ID
28165452Pubmed Central ID
PMC5303823DOI
10.1038/ncomms14252Scopus ID
2-s2.0-85011876562 (requires institutional sign-in at Scopus site) 73 CitationsAbstract
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.
Author List
Mor-Vaknin N, Saha A, Legendre M, Carmona-Rivera C, Amin MA, Rabquer BJ, Gonzales-Hernandez MJ, Jorns J, Mohan S, Yalavarthi S, Pai DA, Angevine K, Almburg SJ, Knight JS, Adams BS, Koch AE, Fox DA, Engelke DR, Kaplan MJ, Markovitz DMAuthor
Julie M. Jorns MD Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAnimals
Aptamers, Nucleotide
Arthritis, Juvenile
Chemotactic Factors
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Disease Models, Animal
Extracellular Traps
Female
Healthy Volunteers
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils
Oncogene Proteins
Poly-ADP-Ribose Binding Proteins
Primary Cell Culture
Synovial Fluid
Zymosan
