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Competitively Inhibited Interaction Of Inflammatory Transcription
                        Factors And Importins By Cell-Permeable Nuclear Localization Sequence
                                            Attenuates The Severity Of COVID-19
                         Dongho Kim, Gyunam Kim, Dasom Shin, Seokwon Lee, Sanghyeon Yu, Misuk Baek, Jaewook Lee,
                           Hyemin Yu, Joohyun Pi, Mingu Kang, Jieun Kim, Sujeong Kim, Eunna Chung and Daewoong Jo
                                    Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea.
                   BACKGROUND                                                   AIM
   The worldwide outbreak of coronavirus disease 19 (COVID-19) is caused  Intracellular delivery of NLS is supposed to suppress expression of
   by infection with the severe acute respiratory syndrome (SARS)-CoV-2  pro-inflammatory cytokines/chemokines by inhibiting transport of
   virus which induces the excessive secretion of pro-inflammatory  IATFs from cytoplasm into nucleus. The cell-permeable NLS namely
   cytokines, known as “cytokine storm”. The uncontrolled production of pro-  iCP-NI regulated expression of cytokines and chemokines. Thus,
   inflammatory cytokine due to SARS-CoV-2 infection can be suppressed  iCP-NI could be developed as a novel anti-inflammatory immune-
   by regulation of nuclear translocation of inflammation-associated  therapeutic agent for severe inflammatory diseases including
   transcription factors (IATFs) such as NF-κB, STAT1/3, AP-1 & NFAT.  COVID-19.
                                                 METHODS
   To prove the therapeutic efficacy of the iCP-NI in COVID-19, acute respiratory distress syndrome (ARDS) mouse models and SARS-CoV-2
   infected golden hamster model were adopted. The LPS, LPS/Poly I:C or SARS-CoV-2 was administrated intratracheally into the animals and
   indicated dosage of iCP-NI were treated following optimized treatment protocols.
                                                 RESULTS























































            CONCLUSION                                REFERENCES                    Contact Information
  iCP-NI significantly attenuates the severity of the SARS-  Chung et al. (2020) Science Advances, 6: eaba 1193  Dongho Kim
  CoV-2 infected syrian hamster model. The reduction of viral  Lim et al. (2013) Clinical Cancer Research, 19: 680-690  Cellivery Therapeutics, Inc.
  replication is proved with quantitative PCR by decreasing the  Lim et al. (2013) Biomaterials, 34: 6261-6271
  level of RdRp gene. Furthermore, the inflammatory cytokine  Lim et al. (2012) Molecular Therapy, 20: 1540-1549  kimdh@cellivery.com
  genes are significantly decreased and the lung structures  Jo et al. (2005) Nature Medicine, 11: 892-898  +82-2-3151-8900
  from inflammation-mediated damages are protected.                                            S4-1 신진과학자
                                            Jo et al. (2001) Nature Biotechnology, 19: 929-933
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