Technologies

The Craik lab at University of California, San Francisco has developed a highly sensitive real-time approach to specifically and accurately detect microscopic blood clots both in vivo and ex vivo. The invention is based on UCSF’s restricted interaction peptides (RIP) platform technology of activatable and detectable membrane interacting peptides that, following activation in the presence of certain proteases, can interact with phospholipid bilayers, such as cell membranes. RIPS have a good safety profile and do not affect hepatic or renal functions.Theseprotease-activated peptide probes can be customized to specific targets and cleaved in the presence of specific proteases, such as thrombin.

To develop a RIP probe for binding and imaging of blood clots, the Craik lab designed a peptide whose sequence is composed of Temporin L followed by the cleavage site and extended interaction sequence from protease-activated receptor-1 (PAR1) and named it PAR1–RIP. Experiments in mice demonstrated that 1) Cy5–PAR1–RIP deposits intensely at the injury site in comparison to an adjacent healthy vessel, 2) PAR1–RIP conjugated to a variety of fluorescent and NIR dyes detected and noninvasively quantified pulmonary emboli (PE) in a dose-dependent manner, 3) achieved Real-time detection and measurement of thrombus generation using PAR1–RIP formulated for NIR fluorescence or PET imaging, and 4) PAR1-RIP clears from circulation in 30 minutes.

This advanced, quantitative, real-time, peptide-based diagnostic technology can provide fast, safe, and highly specific diagnosis, monitoring, and imaging of thrombotic events such as pulmonary embolism, deep vein thrombosis, myocardial infarction and stroke and indirect thrombotic diseases such as cancer and diabetes.