Nucleic-acid based gene therapy approaches for sepsis
Nucleic-acid based gene therapy approaches for sepsis
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DOI：
10.1016/j.ejphar.2018.06.031
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发表时间：
2018-08-15
影响因子：
5
通讯作者：
Matsuda, Naoyuki
中科院分区：
文献类型：
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作者：
Hattori, Yuichi;Hattori, Kohshi;Matsuda, Naoyuki
尽管整体医疗保健有所进步，但败血症及其后遗症仍然是一个令人尴尬的临床实体，死亡率高得令人无法接受。脓毒症及其后遗症的高发病率和高死亡率的主要原因是缺乏有效的治疗。以往的临床试验在很大程度上未能确定一个有效的治疗靶点来改善败血症的临床结果。因此，有利于脓毒症患者预后的关键目标是设计创新和进化的治疗策略。基因治疗被认为是治疗严重疾病最有前途的新方法之一。由于核因子-kappa B （NF-kappa B）和激活蛋白-1 （AP-1）等转录因子在脓毒症的病理生理中起着关键作用，脓毒症可以诱导多种基因及其产物，因此脓毒症可能被视为一种基因相关疾病，基因治疗可能被认为是治疗脓毒症的一种有前景的新治疗方法。在这篇综述文章中，我们提供了最新的基因靶向方法的总结，这些方法已经在败血症的动物模型中发展起来。我们的综述揭示了脓毒症病理的分子基础，为开发新的基因治疗方法提供了基础，并得出结论，未来的研究工作可能会充分考虑到脓毒症的基因治疗。
Despite advances in overall medical care, sepsis and its sequelae continue to be an embarrassing clinical entity with an unacceptably high mortality rate. The central reason for high morbidity and high mortality of sepsis and its sequelae is the lack of an effective treatment. Previous clinical trials have largely failed to identify an effective therapeutic target to improve clinical outcomes in sepsis. Thus, the key goal favoring the outcome of septic patients is to devise innovative and evolutionary therapeutic strategies. Gene therapy can be considered as one of the most promising novel therapeutic approaches for nasty disorders. Since a number of transcription factors, such as nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1), play a pivotal role in the pathophysiology of sepsis that can be characterized by the induction of multiple genes and their products, sepsis may be regarded as a gene-related disorder and gene therapy may be considered a promising novel therapeutic approach for treatment of sepsis. In this review article, we provide an up-to-date summary of the gene-targeting approaches, which have been developed in animal models of sepsis. Our review sheds light on the molecular basis of sepsis pathology for the development of novel gene therapy approaches and leads to the conclusion that future research efforts may fully take into account gene therapy for the treatment of sepsis.