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DOI | 10.1038/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
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ISSN | 2041-1723 |
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 |
URL | 查看原文 |
引用统计 | |
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 |
推荐引用方式 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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