Page 266 - ebook

[E. Immunology] E-2

Intracellular Delivery Of Nuclear Localization Signal Alleviates

Atopic Dermatitis By Regulating The Inflammatory Skin

Environment

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

Eunna Chung¹, Daewoong Jo¹*

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

Atopic dermatitis (AD), which occurs on the skin, is a serious inflammatory autoimmune disease that many people

suffer from. Production of pro-inflammatory cytokines/chemokines is regulated by a certain type of inflammation
associated transcription factors (IAFTs). Improved Cell-Permeable nuclear import inhibitor (iCP-NI) has been

developed by fusing a cyclically-linked NLS of IATFs with advanced macromolecule transduction domain (aMTD), an
sequence optimized hydrophobic cell-penetrating peptide (CPP). iCP-NI suppresses the nuclear transport of IRTFs

by competitatively binding to importin, reducing pro-inflammatory cytokines. To verify the anti-AD efficacy of iCP-
NI cream (w/v, 5%), DNCB (dinitrochlorobenzene)-induced mouse model was used. iCP-NI was delivered into the

epidermal/dermal layers as well as intradermal keratinocyte, following topical administration. Also, iCP-NI restored
1) AD-like skin lesion (50%), as assessed by SCORAD, and 2) the levels of serum IgE (71%), and 3) the expression of

filaggrin protein. Moreover, iCP-NI reduced the upregulated cytokines level such as IL-6 (66%), TNF-α (87%). In
conclusion, these results suggest that iCP-NI has a significant therapeutic effect on AD, an inflammatory skin disease,

through immune system control.