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Development and validation of a small single-domain antibody that effectively inhibits matrix metalloproteinase 8

Delphine Demeestere (UGent) , Eline Dejonckheere (UGent) , Sophie Steeland (UGent) , Paco Hulpiau (UGent) , Jurgen Haustraete (UGent) , Nick Devoogdt, Rielana Wichert, Christoph Becker-Pauly, Elien Van Wonterghem (UGent) , Sylviane Dewaele (UGent) , et al.
(2016) MOLECULAR THERAPY. 24(5). p.890-902
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Abstract
A detrimental role for matrix metalloproteinase 8 (MMP8) has been identified in several pathological conditions, e.g., lethal hepatitis and the systemic inflammatory response syndrome. Since matrix MMP8-deficient mice are protected in the above-mentioned diseases, specific MMP8 inhibitors could be of clinical value. However, targeting a specific matrix metalloproteinase remains challenging due to the strong structural homology of matrix metalloproteinases, which form a family of 25 members in mammals. Single-domain antibodies, called nanobodies, offer a range of possibilities toward therapy since they are easy to generate, express, produce, and modify, e.g., by linkage to nanobodies directed against other target molecules. Hence, we generated small MMP8-binding nanobodies, and established a proof-of-principle for developing nanobodies that inhibit matrix metalloproteinase activity. Also, we demonstrated for the first time the possibility of expressing nanobodies systemically by in vivo electroporation of the muscle and its relevance as a potential therapy in inflammatory diseases.
Keywords
DISEASE, FRAGMENTS, SEPSIS, MICE, LUNG INJURY, SERUM MMP-8, DRUG TARGETS, CRYSTAL-STRUCTURE, NECROSIS-FACTOR-ALPHA, DEFICIENCY

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Chicago
Demeestere, Delphine, Eline Dejonckheere, Sophie Steeland, Paco Hulpiau, Jurgen Haustraete, Nick Devoogdt, Rielana Wichert, et al. 2016. “Development and Validation of a Small Single-domain Antibody That Effectively Inhibits Matrix Metalloproteinase 8.” Molecular Therapy 24 (5): 890–902.
APA
Demeestere, D., Dejonckheere, E., Steeland, S., Hulpiau, P., Haustraete, J., Devoogdt, N., Wichert, R., et al. (2016). Development and validation of a small single-domain antibody that effectively inhibits matrix metalloproteinase 8. MOLECULAR THERAPY, 24(5), 890–902.
Vancouver
1.
Demeestere D, Dejonckheere E, Steeland S, Hulpiau P, Haustraete J, Devoogdt N, et al. Development and validation of a small single-domain antibody that effectively inhibits matrix metalloproteinase 8. MOLECULAR THERAPY. 2016;24(5):890–902.
MLA
Demeestere, Delphine, Eline Dejonckheere, Sophie Steeland, et al. “Development and Validation of a Small Single-domain Antibody That Effectively Inhibits Matrix Metalloproteinase 8.” MOLECULAR THERAPY 24.5 (2016): 890–902. Print.
@article{7898394,
  abstract     = {A detrimental role for matrix metalloproteinase 8 (MMP8) has been identified in several pathological conditions, e.g., lethal hepatitis and the systemic inflammatory response syndrome. Since matrix MMP8-deficient mice are protected in the above-mentioned diseases, specific MMP8 inhibitors could be of clinical value. However, targeting a specific matrix metalloproteinase remains challenging due to the strong structural homology of matrix metalloproteinases, which form a family of 25 members in mammals. Single-domain antibodies, called nanobodies, offer a range of possibilities toward therapy since they are easy to generate, express, produce, and modify, e.g., by linkage to nanobodies directed against other target molecules. Hence, we generated small MMP8-binding nanobodies, and established a proof-of-principle for developing nanobodies that inhibit matrix metalloproteinase activity. Also, we demonstrated for the first time the possibility of expressing nanobodies systemically by in vivo electroporation of the muscle and its relevance as a potential therapy in inflammatory diseases.},
  author       = {Demeestere, Delphine and Dejonckheere, Eline and Steeland, Sophie and Hulpiau, Paco and Haustraete, Jurgen and Devoogdt, Nick and Wichert, Rielana and Becker-Pauly, Christoph and Van Wonterghem, Elien and Dewaele, Sylviane and Van Imschoot, Griet and Aerts, Jeroen and Arckens, Lutgarde and Saeys, Yvan and Libert, Claude and Vandenbroucke, Roosmarijn},
  issn         = {1525-0016},
  journal      = {MOLECULAR THERAPY},
  language     = {eng},
  number       = {5},
  pages        = {890--902},
  title        = {Development and validation of a small single-domain antibody that effectively inhibits matrix metalloproteinase 8},
  url          = {http://dx.doi.org/10.1038/mt.2016.2},
  volume       = {24},
  year         = {2016},
}
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