dNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis

Sangho Lim, Won-Ju Kim, Yeon-Ho Kim, Sohee Lee, Ja-Hyun Koo, Jung-Ah Lee, Heeseok Yoon, Do-Hyun Kim, Hong-Jai Park, Hye-Mi Kim, Hong-Gyun Lee, Ji Yun Kim, Jae-Ung Lee, Jae Hun Shin, Lark Kyun Kim, Junsang Doh, Hongtae Kim, Sang-Kyou Lee, Alfred L. M. Bothwell, Minah Suh and Je-Min Choi ()
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Sangho Lim: College of Natural Sciences, Hanyang University
Won-Ju Kim: College of Natural Sciences, Hanyang University
Yeon-Ho Kim: College of Natural Sciences, Hanyang University
Sohee Lee: Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS)
Ja-Hyun Koo: College of Natural Sciences, Hanyang University
Jung-Ah Lee: College of Natural Sciences, Hanyang University
Heeseok Yoon: College of Natural Sciences, Hanyang University
Do-Hyun Kim: College of Natural Sciences, Hanyang University
Hong-Jai Park: College of Natural Sciences, Hanyang University
Hye-Mi Kim: Pohang University of Science and Technology
Hong-Gyun Lee: College of Natural Sciences, Hanyang University
Ji Yun Kim: College of Natural Sciences, Hanyang University
Jae-Ung Lee: College of Natural Sciences, Hanyang University
Jae Hun Shin: Yale University School of Medicine
Lark Kyun Kim: Yale University School of Medicine
Junsang Doh: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology
Hongtae Kim: Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS)
Sang-Kyou Lee: Yonsei University
Alfred L. M. Bothwell: Yale University School of Medicine
Minah Suh: Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS)
Je-Min Choi: College of Natural Sciences, Hanyang University

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract Central nervous system (CNS)-infiltrating effector T cells play critical roles in the development and progression of multiple sclerosis (MS). However, current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS. Here 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. The dNP2-conjugated cytoplasmic domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows inhibitory effects on experimental autoimmune encephalomyelitis in both preventive and therapeutic mouse models, resulting in the reduction of demyelination and CNS-infiltrating T helper 1 and T helper 17 cells. Thus, this study demonstrates that dNP2 is a blood–brain barrier-permeable peptide and dNP2-ctCTLA-4 could be an effective agent for treating CNS inflammatory diseases such as MS.

Date: 2015
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DOI: 10.1038/ncomms9244

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