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Publications of the Week

Sustained Depletion of FXIII-A by Inducing Acquired FXIII-B Deficiency

By August 7, 2020No Comments

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This week we profile a recent publication in Blood from Amy Wong Strilchuk (pictured)
in the laboratory of Dr. Christian Kastrup at the Michael Smith Laboratories.

Can you provide a brief overview of your lab’s current research focus?

We are working to gain a deeper understanding of how blood clotting is regulated and can be controlled therapeutically. Severe hemorrhage is a major cause of death, particularly among young people, while thrombosis is a major contributor to death and disability with age. We develop novel gene therapy and cell therapy technologies for addressing unmet needs in controlling severe bleeding and preventing unwanted clotting.

What is the significance of the findings in this publication?

This work, describing siRNA targeting FXIII-B (siFXIIIB), is the first pharmacologic approach for long-acting, reversible, and targeted decrease of FXIII-A activity in vivo. It enables the study of FXIII in a wide range of disease models, including in animals not amenable to genetic FXIII knockout. FXIII is considered a therapeutic target for preventing thrombosis, and siFXIIIB overcomes limitations of current antithrombics and thrombolytics by specifically enhancing endogenous fibrinolysis. This agent may be particularly suited to the types of thrombosis and stroke that are occurring in patients with COVID-19.

What are the next steps for this research?

We are using this siRNA agent as a tool to investigate the biological properties of FXIII, and will continue pre-clinical testing of this agent in models of thrombotic disease. We plan to test this agent in models of COVID-19 associated thrombosis. We are also working with several international collaborators to apply this agent in other disease models, ranging from liver dysfunction to multiple sclerosis, to probe the contribution of FXIII and test the agent’s ability to ameliorate symptoms of these diseases.

This work was funded by:

CIHR, NSERC, CanVECTOR

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