PMID- 28178484
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Linking)
VI  - 16
IP  - 7
DP  - 2008 Jul
TI  - An Endogenous TNF-alpha Antagonist Induced by Splice-switching Oligonucleotides 
      Reduces Inflammation in Hepatitis and Arthritis Mouse Models.
PG  - 1316-1322
LID - S1525-0016(16)32473-X [pii]
LID - 10.1038/mt.2008.85 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a key mediator of inflammatory diseases, 
      including rheumatoid arthritis (RA), and anti-TNF-alpha drugs such as etanercept are 
      effective treatments. Splice-switching oligonucleotides (SSOs) are a new class of 
      drugs designed to induce therapeutically favorable splice variants of targeted 
      genes. In this work, we used locked nucleic acid (LNA)-based SSOs to modulate 
      splicing of TNF receptor 2 (TNFR2) pre-mRNA. The SSO induced skipping of TNFR2 
      exon 7, which codes the transmembrane domain (TM), switching endogenous 
      expression from the membrane-bound, functional form to a soluble, secreted form 
      (Delta7TNFR2). This decoy receptor protein accumulated in the circulation of treated 
      mice, antagonized TNF-alpha, and altered disease in two mouse models: TNF-alpha-induced 
      hepatitis and collagen-induced arthritis (CIA). This is the first report of 
      upregulation of the endogenous, circulating TNF-alpha antagonist by 
      oligonucleotide-induced splicing modulation.
CI  - Copyright (c) 2008 The American Society of Gene Therapy. Published by Elsevier Inc. 
      All rights reserved.
FAU - Graziewicz, Maria A
AU  - Graziewicz MA
AD  - Ercole Biotech, Inc., Research Triangle Park, North Carolina, USA.
FAU - Tarrant, Teresa K
AU  - Tarrant TK
AD  - Division of Rheumatology, Allergy and Immunology, Department of Medicine, 
      University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
FAU - Buckley, Brian
AU  - Buckley B
AD  - Ercole Biotech, Inc., Research Triangle Park, North Carolina, USA.
FAU - Roberts, Jennifer
AU  - Roberts J
AD  - Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel 
      Hill, North Carolina, USA; Lineberger Comprehensive Cancer Center, University of 
      North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
FAU - Fulton, LeShara
AU  - Fulton L
AD  - Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel 
      Hill, North Carolina, USA; Lineberger Comprehensive Cancer Center, University of 
      North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
FAU - Hansen, Henrik
AU  - Hansen H
AD  - Santaris Pharma, Horsholm, Denmark.
FAU - Orum, Henrik
AU  - Orum H
AD  - Santaris Pharma, Horsholm, Denmark.
FAU - Kole, Ryszard
AU  - Kole R
AD  - Ercole Biotech, Inc., Research Triangle Park, North Carolina, USA; Department of 
      Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North 
      Carolina, USA; Lineberger Comprehensive Cancer Center, University of North 
      Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
FAU - Sazani, Peter
AU  - Sazani P
AD  - Ercole Biotech, Inc., Research Triangle Park, North Carolina, USA. Electronic 
      address: sazani@ercolebiotech.com.
LA  - eng
PT  - Journal Article
DEP - 20161208
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
EDAT- 2008/07/01 00:00
MHDA- 2008/07/01 00:01
CRDT- 2017/02/09 06:00
PHST- 2008/02/04 00:00 [received]
PHST- 2008/04/02 00:00 [accepted]
PHST- 2017/02/09 06:00 [entrez]
PHST- 2008/07/01 00:00 [pubmed]
PHST- 2008/07/01 00:01 [medline]
AID - S1525-0016(16)32473-X [pii]
AID - 10.1038/mt.2008.85 [doi]
PST - ppublish
SO  - Mol Ther. 2008 Jul;16(7):1316-1322. doi: 10.1038/mt.2008.85. Epub 2016 Dec 8.