Hanyang UniversityOpportunity Contact
James Noh, CEO
Seoul, South Korea

Hanyang University Website
TherapeuticPreclinical Pharmalicensing.com

We identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues.

Introduction/Background
We identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues. Moreover, it enters the brain tissue and resident cells through blood vessels by penetrating the tightly organized blood–brain barrier. Then, we developed cytoplasmic domain of CTLA-4 (ctCTLA-4) peptide without its ligand interacting domain by conjugating BBB-penetrating peptide, dNP2 (dNP2-ctCTLA-4). We found that this dNP2-ctCTLA-4 could be able to induce Foxp3 expression in T cells which is important marker for regulatory T cells dependent on TGF-β. Moreover, dNP2-ctCTLA-4 treatment in vivo remarkably controls EAE progression by increase of Treg cells, which assures prolonged suppression of disease relapse.


Description of Technology

Technique 1: Novel blood-brain barrier-penetrating peptide, dNP2.

dNP2 is a novel 24-amino acids in length BBB-penetrating peptide of human origin.

Protein delivery efficiency of dNP2 in brain and spinal cord. (a) Mouse brains were observed at 40 min after injection via multi-photon confocal microscopy using a 3D lateral view and 3D top view or magnified 3D top view. (b) The fluorescent diffusion of the dNP2-dTomato protein out of blood vessels in the brain was monitored from 20–120 min. (c) Co-localization of the dNP2-dTomato (red) signal with fluorescent signals specific for various cell types, including neurons (NeuN, green), astrocytes(GFAP, green), and microglia (Iba-1, green). White boxes in the merged images are magnified regions. (d) The cellular localization of the dNP2-dTomato protein in the brain or spinal cord tissues in EAE mouse model. (e) The co-localization of the dNP2-dTomato protein with CD4-positive cells (green).

Technique 2: Regulatory T cell inducing drug candidate for multiple sclerosis therapy.

dNP2-ctCTLA-4 was constructed by conjugating BBB-penetrating peptide, dNP2, and cytoplasmic domain of CTLA-4 protein.

dNP2-ctCTLA-4 inhibited the T cell activation and proliferation in both mouse and human CD4 T cells upon anti-CD3/28 TCR stimulation.

Treatment of dNP2-ctCTLA-4 converts Th17 to Foxp3-expressing Tregs and dNP2-ctCTLA-4-induced Foxp3+ T cells showed similar characteristics with iTreg at transcript level.

Foxp3-expressing Tregs were increased and both IFNγ-expressing Th1 and IL-17-expressing Th17 cells were significantly reduced by administration of dNP2-ctCTLA-4 in the spinal cord of EAE-induced mouse.

Administration of dNP2-ctCTLA-4 effectively suppressed relapse in relapse-remitting EAE model.

Type of Business Relationship Sought
Out license, Partnership


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