Page 264 - ebook

[E. Immunology] E-1

Hydrophobic Cell Penetrating Peptide-Combined Nuclear

Localization Signal Suppresses Pro-Inflammatory Cytokines In

Inflammatory Bowel Disease

Seokwon Lee¹, Jaehyeon Kim¹, Hyunji Lee¹, Hyeontae Kang¹, Mingu Kang¹, Eunhee Yang¹,

Eunna Chung¹, Daewoong Jo¹*

¹Immune Disease Team, Cellivery Therapeutics, Inc., Seoul 03929, Korea

Inflammatory bowel disease (IBD) includes two types of inflammatory diseases, ulcerative colitis (UC) and Crohn’s

disease (CD). To target the IBD, hydrophobic cell penetrating peptide-combined nuclear localization signal (NLS)
was used, as named improved Cell-Permeable nuclear import inhibitor (iCP-NI). The NLS of iCP-NI was adopted

from NF-κB, and then cyclized for enhancement of in vivo stability. iCP-NI competitively binds to the importins, the
nuclear transporter, and suppresses the nuclear import of transcription factors upregulating the cytokines. The

efficacy of iCP-NI against IBD was evaluated in two different animal models by intrarectal administration of iCP-NI.
In dextran sulfate sodium (DSS)-induced UC mouse model, iCP-NI recovered the shortened small intestine by 31%

(compare to the vehicle group), and the inflammatory lesions were also diminished, resulting the restoration of
destructured epithelium of small intestine. For the 2, 4, 6-trinitrobenzenesulfonic acid solution (TNBS)-induced CD

mouse model, the pathological score (i.e. edema, ulcer, and vascular congestion) was also decreased by 71%, and
the internal layer of intestine was restructured. Additionally, the pro-inflammatory cytokines, such as TNF-α, IFN-γ,

and IL-6, were reduced in the blood stream by 64%, 97%, and 72%, respectively. Based on the above-described
anti-inflammatory effects of iCP-NI, iCP-NI can be a powerful next-generation.