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Development and Validation of a Small Single-domain Antibody That Effectively Inhibits Matrix Metalloproteinase 8
- Source :
- Molecular Therapy. 24:890-902
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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.Molecular Therapy (2016); doi:10.1038/mt.2016.2.
- Subjects :
- 0301 basic medicine
Matrix metalloproteinase inhibitor
Matrix Metalloproteinase Inhibitors
Lung injury
Matrix (biology)
Biology
Matrix metalloproteinase
MMP8
Mice
03 medical and health sciences
In vivo
Drug Discovery
Genetics
Animals
Molecular Biology
Inflammation
Mice, Knockout
Pharmacology
Electroporation
Single-Domain Antibodies
Molecular biology
Cell biology
Molecular Docking Simulation
Disease Models, Animal
Matrix Metalloproteinase 8
030104 developmental biology
Single-domain antibody
Molecular Medicine
Original Article
Subjects
Details
- ISSN :
- 15250016
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy
- Accession number :
- edsair.doi.dedup.....5c4c111763750e88c1fb00c5799d9645