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 SuhJe Min Choi

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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.

Original languageEnglish
Article number8244
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Sep 15

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Lim, S., Kim, W. J., Kim, Y. H., Lee, S., 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., Kim, H., Lee, S. K., Bothwell, A. L. M., ... Choi, J. M. (2015). dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis. Nature communications, 6, [8244]. https://doi.org/10.1038/ncomms9244