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Systemically-Delivered Nuclear Localization Signal Has
Therapeutic Potential To Treat Sepsis By Suppressing Cytokine-Storm

Gyunam Kim, Dongho Kim, Sanghyeon Yu, Misuk Baek, Jaewook Lee, Eunna Chung and Daewoong Jo
Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea.

BACKGROUND AIM
Infection activates innate immunity to generate pro-inflammatory This study suggests that improved Cell-Permeable nuclear import
cytokines and cause inflammation. However, dysregulated expression inhibitor (iCP-NI) has potential as a novel medicine to cure sepsis
of cytokines rather damages multiple organs, can lead to death. This which accompanies severe inflammatory disorder caused by
condition is called sepsis, and it is important to control inflammation. excessive secretion of pro-inflammatory cytokines & chemokines.

METHODS
To regulate the uncontrolled cytokines, iCP-NI has been developed by fusing hydrophobic cell-penetrating peptide with NLS, and demonstrated
its improved therapeutic applicability. Cell-permeability of iCP-NI were verified by pull-down assay. To investigate the anti-inflammatory effect of
iCP-NI, 1) IATFs nuclear translocation in macrophages treated with LPS/IFN-γ was confirmed by confocal microscopy and WB, and 2) cytokine
expression was confirmed by qRT-PCR and ELISA. To prove the efficacy of iCP-NI in sepsis, peritonitis models were developed by cecal slurry
(CS) injection and cecal ligation and puncture (CLP) surgery. These peritonitis mice were administered with iCP-NI & meropenem intravenously.

RESULTS

CONCLUSION REFERENCES Contact information

iCP-NI has superior cell/tissue-permeability and directly binds with Rittirsch et al. (2009) Nature Protocols, 4, 31-36
Dongho Kim
importin α5. Therefore, iCP-NI regulates inflammatory cytokines by
Deng et al. (2018) Inflammation, 41.6: 2101-0109
inhibiting the nuclear translocation of IATFs. iCP-NI increased Cellivery Therapeutics, Inc.
Jo et al. (2005) Nature Medicine, 11(8):892-8
survivability of hepatitis & sepsis animals. These results suggest
Kimdh@cellivery.com
that iCP-NI has the potential as a novel drug to cure various acute Chen et al. (2020) Shock, 53(6): 761-771
inflammatory diseases, which accompany severe inflammatory Abraham et al. (2018) Crit. Care. Med., 46(8):e797-e804 +82-2-3151-8900
disorder and cytokine-storm.