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

Title
dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis
Author
최제민
Keywords
DISEASE-MODIFYING THERAPIES; CELL-PENETRATING PEPTIDES; VECTOR-MEDIATED STRATEGY; MULTIPLE-SCLEROSIS; TRANSDUCTION DOMAIN; T-CELLS; CYTOPLASMIC DOMAIN; HEPARAN-SULFATE; FUSION PROTEINS; INNATE IMMUNITY
Issue Date
2015-09
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE COMMUNICATIONS, v. 6, Article no. 8244
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.
URI
https://www.nature.com/articles/ncomms9244http://hdl.handle.net/20.500.11754/27514
ISSN
2041-1723
DOI
10.1038/ncomms9244
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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