Researchers from the Institute of Cardiovascular Sciences at the University of Birmingham, UK, have produced the first binding molecules (ligands) of defined composition to make platelets clump together in a predictable way.
The research team, led by Professor Steve Watson and Dr Eleyna Martin, developed antibody fragments called nanobodies and crosslinked these to make ligands to four platelet receptors (GPVI, CLEC-2, FcɣRIIA and PEAR1).
The nanobodies can be used to develop validated clinical assays for testing patients with platelet disorders such as bleeding or thrombosis, and as research tools to study platelet activation.
Professor Watson said: “Nanobodies have the same properties as antibodies but have several inherent advantages for platelet researchers. They are smaller, which makes them more suitable for cross-linking, and this size, coupled with their stability and high affinity for platelet receptors, makes them ideal reagents for receptor imaging.”
Research in this area has been hampered due to limitations of the currently used ligands. Some have undefined valency (binding power), while others, such as the snake venom toxin rhodocytin, show significant batch variation, or uncertain specificity for the receptors.
The Birmingham researchers developed nanobodies with one, two, three and four binding sites, and tested the ability of these to generate signalling molecules and stimulate platelet activation.
Professor Watson added: “We are entering an exciting period in thrombosis research. Reagents based on nanobodies will increase our understanding of platelet activation in the laboratory. Although nanobodies have a short half-life in vivo, this could be counteracted by linkage to larger inert molecules and yield novel therapeutics for blood and thrombotic disorders.”