GSTDTAP  > 资源环境科学
DOI10.1038/s41467-017-01628-8
RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome
Urak, Kevin T.1,2; Blanco, Giselle N.1; Shubham, Shambhavi1; Lin, Li-Hsien1; Dassie, Justin P.1; Thiel, William H.1,3; Chen, Yani1; Sonkar, Vijay Kumar1; Lei, Beilei4; Murthy, Shubha1; Gutierrez, Wade R.5; Wilson, Mary E.1,6,7; Stiber, Jonathan A.4; Klesney-Tait, Julia1; Dayal, Sanjana1; Miller, Francis J., Jr.4,8,9; Giangrande, Paloma H.1,2,3,10,11,12,13
2019-01-10
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
出版年2019
卷号10
文章类型Article
语种英语
国家USA
英文摘要

The development of multiple organ dysfunction syndrome (MODS) following infection or tissue injury is associated with increased patient morbidity and mortality. Extensive cellular injury results in the release of nuclear proteins, of which histones are the most abundant, into the circulation. Circulating histones are implicated as essential mediators of MODS. Available anti-histone therapies have failed in clinical trials due to off-target effects such as bleeding and toxicity. Here, we describe a therapeutic strategy for MODS based on the neutralization of histones by chemically stabilized nucleic acid bio-drugs (aptamers). Systematic evolution of ligands by exponential enrichment technology identified aptamers that selectively bind those histones responsible for MODS and do not bind to serum proteins. We demonstrate the efficacy of histone-specific aptamers in human cells and in a murine model of MODS. These aptamers could have a significant therapeutic benefit in the treatment of multiple diverse clinical conditions associated with MODS.


领域资源环境
收录类别SCI-E
WOS记录号WOS:000455354800013
WOS关键词NEUTROPHIL EXTRACELLULAR TRAPS ; HISTONE-INDUCED DAMAGE ; ANTI-VEGF APTAMER ; CIRCULATING HISTONES ; IN-VITRO ; MAMMALIAN EPITHELIUM ; MAJOR MEDIATORS ; RISK-FACTORS ; CELLS ; COAGULATION
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
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文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/203513
专题资源环境科学
作者单位1.Univ Iowa, Internal Med, Iowa City, IA 52242 USA;
2.Univ Iowa, Mol & Cellular Biol Program, Iowa City, IA 52242 USA;
3.Univ Iowa, Abboud Cardiovasc Res Ctr, Iowa City, IA 52242 USA;
4.Duke Univ, Dept Med, Durham, NC 27708 USA;
5.Univ Iowa, Med Scientist Training Program, Iowa City, IA 52242 USA;
6.Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA;
7.Univ Iowa, Vet Affairs Med Ctr, Iowa City, IA 52241 USA;
8.Duke Univ, Pharmacol & Canc Biol Program, Durham, NC 27708 USA;
9.Vet Adm Med Ctr, Dept Med, Durham, NC 27705 USA;
10.Univ Iowa, Interdisciplinary Grad Program Genet, Iowa City, IA 52242 USA;
11.Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA;
12.Univ Iowa, Radiat Oncol, Iowa City, IA 52242 USA;
13.Univ Iowa, EHSRC, Iowa City, IA 52242 USA
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GB/T 7714
Urak, Kevin T.,Blanco, Giselle N.,Shubham, Shambhavi,et al. RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome[J]. NATURE COMMUNICATIONS,2019,10.
APA Urak, Kevin T..,Blanco, Giselle N..,Shubham, Shambhavi.,Lin, Li-Hsien.,Dassie, Justin P..,...&Giangrande, Paloma H..(2019).RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome.NATURE COMMUNICATIONS,10.
MLA Urak, Kevin T.,et al."RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome".NATURE COMMUNICATIONS 10(2019).
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