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

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Title
dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis
Author(s)
Lim, S.; Kim, W.-J.; Kim, Y.-H.; Sohee Lee; Koo, J.-H.; Lee, J.-A.; Yoon, H.; Kim, D.-H.; Park, H.-J.; Kim, H.-M.; Lee, H.-G.; Yun Kim, J.; Lee, J.-U.; Hun Shin, J.; Kyun Kim, L.; Doh, J.; Hongtae Kim; Lee, S.-K.; Bothwell, A.L.M.; Minah Suh; Je-Min Choi
Publication Date
2015-09
Journal
NATURE COMMUNICATIONS, v.6, pp.8244
Publisher
NATURE PUBLISHING GROUP
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. © 2015 Macmillan Publishers Limited. All rights reserved
URI
https://pr.ibs.re.kr/handle/8788114/1901
DOI
10.1038/ncomms9244
ISSN
2041-1723
Appears in Collections:
Center for Neuroscience Imaging Research (뇌과학 이미징 연구단) > 1. Journal Papers (저널논문)
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