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

Nature Communications

Volumn 6, Issue , 2015, Pages

  Lim, Sangho ^a   Kim, Won Ju ^a   Kim, Yeon Ho ^a   Lee, Sohee ^b,c   Koo, Ja Hyun ^a   Lee, Jung Ah ^a   Yoon, Heeseok ^a   Kim, Do Hyun ^a   Park, Hong Jai ^a   Kim, Hye Mi ^d   Lee, Hong Gyun ^a   Yun Kim, Ji ^a   Lee, Jae Ung ^a   Hun Shin, Jae ^e   Kyun Kim, Lark ^e   Doh, Junsang ^d   Kim, Hongtae ^b,f   Lee, Sang Kyou ^g   Bothwell, Alfred L M ^e   Suh, Minah ^b,c,f   Choi, Je Min ^a,b   more..

^a Hanyang University   (South Korea)

^b Institute for Basic Science   (South Korea)

^c Samsung Advanced Institute of Technology (SAIT)   (South Korea)

^d Pohang University of Science and Technology (POSTECH)   (South Korea)

^e YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f Sungkyunkwan University   (South Korea)

^g Yonsei University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOPLASMIC DOMAIN OF CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; NEUROPROTECTIVE AGENT; PEPTIDE DERIVATIVE; RECOMBINANT DNP2; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG; CARRIER PROTEIN; CELL PENETRATING PEPTIDE; DNP2 PEPTIDE; PEPTIDE FRAGMENT; UBIQUITIN PROTEIN LIGASE; UFL1 PROTEIN, HUMAN;

BLOOD; CYTOLOGY; CYTOPLASM; DRUG; EXPERIMENTAL STUDY; IMMUNE RESPONSE; PEPTIDE; PERMEABILITY; PROTEIN; RODENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; CD4+ T LYMPHOCYTE; CELL PERMEABILIZATION; CENTRAL NERVOUS SYSTEM; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DEMYELINATION; DRUG CONJUGATION; DRUG PENETRATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FEMALE; FLUORESCENCE MICROSCOPY; HELA CELL LINE; HUMAN; HUMAN CELL; INFLAMMATORY DISEASE; MOUSE; MOUSE MODEL; MULTIPLE SCLEROSIS; NEUROPROTECTION; NONHUMAN; T LYMPHOCYTE; TANDEM REPEAT; TH1 CELL; TH17 CELL; ANIMAL; C57BL MOUSE; DISEASE MODEL; IMMUNOLOGY; IN VITRO STUDY; JURKAT CELL LINE; METABOLISM;

ANIMALS; BLOOD-BRAIN BARRIER; CARRIER PROTEINS; CELL-PENETRATING PEPTIDES; CTLA-4 ANTIGEN; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; HELA CELLS; HUMANS; IN VITRO TECHNIQUES; JURKAT CELLS; MICE; MICE, INBRED C57BL; PEPTIDE FRAGMENTS; T-LYMPHOCYTES; TH17 CELLS; UBIQUITIN-PROTEIN LIGASES;

EID: 84941758039     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms9244     Document Type: Article

References (70)

1. Trapp, B. D., Ransohoff, R. & Rudick, R. Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr. Opin. Neurol. 12, 295-302 (1999).
2. Rangachari, M. & Kuchroo, V. K. Using EAE to better understand principles of immune function and autoimmune pathology. J. Autoimmun. 45, 31-39 (2013).
3. Goverman, J. Autoimmune T cell responses in the central nervous system. Nat. Rev. Immunol. 9, 393-407 (2009).
4. Pierson, E., Simmons, S. B., Castelli, L. & Goverman, J. M. Mechanisms regulating regional localization of inflammation during CNS autoimmunity. Immunol. Rev. 248, 205-215 (2012).
5. Wingerchuk, D. M. & Carter, J. L. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin. Proc. 89, 225-240 (2014).
6. Tavazzi, E., Rovaris, M. & La Mantia, L. Drug therapy for multiple sclerosis. Can. Med. Assoc. J. 186, 833-840 (2014).
7. Chen, Y. & Liu, L. Modern methods for delivery of drugs across the blood-brain barrier. Adv. Drug Deliv. Rev. 64, 640-665 (2012).
8. Mackic, J. B. et al. Cereport (RMP-7) increases the permeability of human brain microvascular endothelial cell monolayers. Pharm. Res. 16, 1360-1365 (1999).
9. Bidanset, D. J. et al. Intravenous infusion of cereport increases uptake and efficacy of acyclovir in herpes simplex virus-infected rat brains. Antimicrob. Agents Chemother. 45, 2316-2323 (2001).
10. Hynynen, K. Ultrasound for drug and gene delivery to the brain. Adv. Drug Deliv. Rev. 60, 1209-1217 (2008).
11. Cao, G. et al. In vivo delivery of a Bcl-xL fusion protein containing the TAT protein transduction domain protects against ischemic brain injury and neuronal apoptosis. J. Neurosci. 22, 5423-5431 (2002).
12. Kilic, E., Dietz, G. P., Hermann, D. M. & Bahr, M. Intravenous TAT-Bcl-Xl is protective after middle cerebral artery occlusion in mice. Ann. Neurol. 52, 617-622 (2002).
13. Rousselle, C. et al. New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vector-mediated strategy. Mol. Pharmacol. 57, 679-686 (2000).
14. Rousselle, C., Clair, P., Temsamani, J. & Scherrmann, J. M. Improved brain delivery of benzylpenicillin with a peptide-vector-mediated strategy. J. Drug Target. 10, 309-315 (2002).
15. Rousselle, C. et al. Improved brain uptake and pharmacological activity of dalargin using a peptide-vector-mediated strategy. J. Pharmacol. Exp. Ther. 306, 371-376 (2003).
16. Walunas, T. L. et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity 1, 405-413 (1994).
17. Krummel, M. F. & Allison, J. P. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J. Exp. Med. 182, 459-465 (1995).
18. Linsley, P. S. et al. CTLA-4 is a second receptor for the B cell activation antigen B7. J. Exp. Med. 174, 561-569 (1991).
19. Lee, K. M. et al. Molecular basis of T cell inactivation by CTLA-4. Science 282, 2263-2266 (1998).
20. Valk, E., Rudd, C. E. & Schneider, H. CTLA-4 trafficking and surface expression. Trends Immunol. 29, 272-279 (2008).
21. Vijayakrishnan, L. et al. An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells. Immunity 20, 563-575 (2004).
22. Choi, J. M. et al. Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation. Nat. Med. 12, 574-579 (2006).
23. Choi, J. M. et al. Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis. Proc. Natl Acad. Sci. USA 105, 19875-19880 (2008).
24. Kim, C. H. et al. Overexpression of a novel regulator of p120 catenin, NLBP, promotes lung adenocarcinoma proliferation. Cell Cycle 12, 2443-2453 (2013).
25. Kwon, J. et al. A novel LZAP-binding protein, NLBP, inhibits cell invasion. J. Biol. Chem. 285, 12232-12240 (2010).
26. Lim, S., Kim, W. J., Kim, Y. H. & Choi, J. M. Identification of a novel cell-penetrating peptide from human phosphatidate phosphatase LPIN3. Mol. Cells 34, 577-582 (2012).
27. van den Berg, A. & Dowdy, S. F.Protein transduction domain delivery of therapeutic macromolecules. Curr. Opin. Biotechnol. 22, 888-893 (2011).
28. Yan, H. et al. Expression and purification of human TAT-p53 fusion protein in Pichia pastoris and its influence on HepG2 cell apoptosis. Biotechnol. Lett. 34, 1217-1223 (2012).
29. Rothbard, J. B. et al. Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation. Nat. Med. 6, 1253-1257 (2000).
30. Simon, M. J., Gao, S., Kang, W. H., Banta, S. & Morrison, 3rd B. TAT-mediated intracellular protein delivery to primary brain cells is dependent on glycosaminoglycan expression. Biotechnol. Bioeng. 104, 10-19 (2009).
31. Ziegler, A. Thermodynamic studies and binding mechanisms of cell-penetrating peptides with lipids and glycosaminoglycans. Adv. Drug Deliv. Rev. 60, 580-597 (2008).
32. Gump, J. M., June, R. K. & Dowdy, S. F. Revised role of glycosaminoglycans in TAT protein transduction domain-mediated cellular transduction. J. Biol. Chem. 285, 1500-1507 (2010).
33. Richard, J. P. et al. Cellular uptake of unconjugated TAT peptide involves clathrin-dependent endocytosis and heparan sulfate receptors. J. Biol. Chem. 280, 15300-15306 (2005).
34. West, M. A., Bretscher, M. S. & Watts, C. Distinct endocytotic pathways in epidermal growth factor-stimulated human carcinoma A431 cells. J. Cell Biol. 109, 2731-2739 (1989).
35. Kaplan, I. M., Wadia, J. S. & Dowdy, S. F. Cationic TAT peptide transduction domain enters cells by macropinocytosis. J. Control. Release 102, 247-253 (2005).
36. Frankel, A. D. & Pabo, C. O. Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55, 1189-1193 (1988).
37. Schwarze, S. R., Ho, A., Vocero-Akbani, A. & Dowdy, S. F. In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285, 1569-1572 (1999).
38. Derossi, D., Joliot, , Chassaing, G. & Prochiantz, A. The third helix of the Antennapedia homeodomain translocates through biological membranes. J. Biol. Chem. 269, 10444-10450 (1994).
39. Morris, M. C., Depollier, J., Mery, J., Heitz, F. & Divita, G. A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat. Biotechnol. 19, 1173-1176 (2001).
40. Elliott, G. & O'Hare, P. Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell 88, 223-233 (1997).
41. Wender, P. A. et al. The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transporters. Proc. Natl Acad. Sci. USA 97, 13003-13008 (2000).
42. Meade, B. R. & Dowdy, S. F. Exogenous siRNA delivery using peptide transduction domains/cell penetrating peptides. Adv. Drug Deliv. Rev. 59, 134-140 (2007).
43. Moschos, S. A. et al. Lung delivery studies using siRNA conjugated to TAT (48-60) and penetratin reveal peptide induced reduction in gene expression and induction of innate immunity. Bioconj. Chem. 18, 1450-1459 (2007).
44. Arthanari, Y., Pluen, A., Rajendran, R., Aojula, H. & Demonacos, C. Delivery of therapeutic shRNA and siRNA by Tat fusion peptide targeting BCR-ABL fusion gene in Chronic Myeloid Leukemia cells. J. Control. Release 145, 272-280 (2010).
45. Lee, J. et al. Activation of innate immunity is required for efficient nuclear reprogramming. Cell 151, 547-558 (2012).
46. Koren, E. & Torchilin, V. P. Cell-penetrating peptides: breaking through to the other side. Trends Mol. Med. 18, 385-393 (2012).
47. Chen, L. & Harrison, S. D. Cell-penetrating peptides in drug development: enabling intracellular targets. Biochem. Soc. Trans. 35, 821-825 (2007).
48. Eguchi, A. et al. Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein. Nat. Biotechnol. 27, 567-571 (2009).
49. Geoghegan, J. C., Gilmore, B. L. & Davidson, B. L. Gene silencing mediated by siRNA-binding fusion proteins is attenuated by double-stranded RNA-binding domain structure. Mol. Ther. Nucleic Acids 1, e53 (2012).
50. Abudara, V. et al. The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes. Front. Cell. Neurosci. 8, 306 (2014).
51. Parton, R. G. & Dotti, C. G. Cell biology of neuronal endocytosis. J. Neurosci. Res. 36, 1-9 (1993).
52. Sokolowski, J. D. & Mandell, J. W. Phagocytic clearance in neurodegeneration.Am. J. Pathol. 178, 1416-1428 (2011).
53. Wadia, J. S., Stan, R. V. & Dowdy, S. F. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat. Med. 10, 310-315 (2004).
54. Ziegler, A. & Seelig, J. Interaction of the protein transduction domain of HIV-1 TAT with heparan sulfate: binding mechanism and thermodynamic parameters. Biophys. J. 86, 254-263 (2004).
55. Herve, F., Ghinea, N. & Scherrmann, J. M. CNS delivery via adsorptive transcytosis. AAPS J. 10, 455-472 (2008).
56. Zhang, Y. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 9, 40 (2008).
57. Roy, A., Kucukural, A. & Zhang, Y. I-TASSER: a unified platform for automated protein structure and function prediction.Nat. Protoc. 5, 725-738 (2010).
58. Dhib-Jalbut, S. & Marks, S. Interferon-beta mechanisms of action in multiple sclerosis. Neurology 74(Suppl 1): S17-S24 (2010).
59. Arnon, R. & Aharoni, R. Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications. Proc. Natl Acad. Sci. USA 101(Suppl 2): 14593-14598 (2004).
60. Steinman, L. Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab. Nat. Rev. Drug. Discov. 4, 510-518 (2005).
61. Brinkmann, V. et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors.J. Biol. Chem. 277, 21453-21457 (2002).
62. Kim, W., Zandona, M. E., Kim, S. H. & Kim, H. J. Oral disease-modifying therapies for multiple sclerosis. J. Clin. Neurol. 11, 9-19 (2015).
63. English, C. & Aloi, J. J. New FDA-approved disease-modifying therapies for multiple sclerosis. Clin. Ther. 37, 691-715 (2015).
64. Kappos, L. et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N. Engl. J. Med. 362, 387-401 (2010).
65. Chikuma, S., Abbas, A. K. & Bluestone, J. A. B7-independent inhibition of T cells by CTLA-4. J. Immunol. 175, 177-181 (2005).
66. Stumpf, M., Zhou, X. & Bluestone, J. A. The B7-independent isoform of CTLA-4 functions to regulate autoimmune diabetes. J. Immunol. 190, 961-969 (2013).
67. Araki, M. et al. Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice. J. Immunol. 183, 5146-5157 (2009).
68. Liu, S. M. et al. Overexpression of the Ctla-4 isoform lacking exons 2 and 3 causes autoimmunity. J. Immunol. 188, 155-162 (2012).
69. Ichinose, K. et al. Brief report: increased expression of a short splice variant of CTLA-4 exacerbates lupus in MRL/lpr mice. Arthritis Rheum. 65, 764-769 (2013).
70. Ueda, H. et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423, 506-511 (2003).