Ben-Nun-Shaul Orly, Srivastava Rohit, Elgavish Sharona, Gandhi Shashi, Nevo Yuval, Benyamini Hadar, Eden Arieh, Oppenheim Ariella
Department of Hematology, Hadassah Medical Center, Jerusalem, Israel.
The Hebrew University Faculty of Medicine, Jerusalem, Israel.
Oncotarget. 2020 Feb 11;11(6):574-588. doi: 10.18632/oncotarget.27448.
Sepsis is an excessive, dysregulated immune response to infection that activates inflammatory and coagulation cascades, which may lead to tissue injury, multiple organ dysfunction syndrome and death. Millions of individuals die annually of sepsis. To date, the only treatment available is antibiotics, drainage of the infection source when possible, and organ support in intensive care units. Numerous previous attempts to develop therapeutic treatments, directed at discreet targets of the sepsis cascade, could not cope with the complex pathophysiology of sepsis and failed. Here we describe a novel treatment, based on empty capsids of SV40 (nanocapsids - NCs). Studies in a severe rat sepsis model showed that pre-treatment by NCs led to a dramatic increase in survival, from zero to 75%. Transcript analyses (RNAseq) demonstrated that the NC treatment is a paradigm shift. The NCs affect multiple facets of biological functions. The affected genes are modified with time, adjusting to the recovery processes. The NCs effect on normal control rats was negligible. The study shows that the NCs are capable of coping with diseases with intricate pathophysiology. Further studies are needed to determine whether when applied after sepsis onset, the NCs still improve outcome.
脓毒症是对感染产生的过度、失调的免疫反应，会激活炎症和凝血级联反应，这可能导致组织损伤、多器官功能障碍综合征和死亡。每年有数百万人死于脓毒症。迄今为止，唯一可用的治疗方法是使用抗生素、尽可能引流感染源以及在重症监护病房进行器官支持。此前针对脓毒症级联反应的离散靶点进行治疗的众多尝试，都无法应对脓毒症复杂的病理生理学，均以失败告终。在此，我们描述一种基于SV40空衣壳（纳米衣壳 - NCs）的新型治疗方法。在严重大鼠脓毒症模型中的研究表明，用NCs进行预处理可使存活率大幅提高，从零提升至75%。转录组分析（RNAseq）表明，NC治疗是一种范式转变。NCs影响生物功能的多个方面。受影响的基因会随时间发生改变，以适应恢复过程。NCs对正常对照大鼠的影响可忽略不计。该研究表明，NCs能够应对具有复杂病理生理学的疾病。还需要进一步研究以确定在脓毒症发作后应用NCs时，是否仍能改善预后。
