Empty SV40 capsids increase survival of septic rats by eliciting numerous host signaling networks that participate in a number of systemic functions
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Orly Ben-Nun-Shaul1,*, Rohit Srivastava2,*, Sharona Elgavish3, Shashi Gandhi2, Yuval Nevo3, Hadar Benyamini3, Arieh Eden4 and Ariella Oppenheim2
1 Department of Hematology, Hadassah Medical Center, Jerusalem, Israel
2 The Hebrew University Faculty of Medicine, Jerusalem, Israel
3 Bioinformatics Unit of the I-CORE Computation Center, The Hebrew University and Hadassah Medical Center, Jerusalem, Israel
4 Department of Anesthesiology, Critical Care and Pain Medicine, Lady Davis Carmel Medical Center, Haifa, Israel
* These authors contributed equally to this work
Keywords: sepsis; empty SV40 capsids; RNAseq; signaling; cellular functions
Received: November 14, 2019 Accepted: December 26, 2019 Published: February 11, 2020
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.
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