Kate Nesbitt
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Kate Nesbitt has a total of 20 co-authors. Here are the top co-authors by number of shared publications:
- Alisa S. Wolberg
Department of Pathology and Laboratory Medicine and UNC Blood Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC
1 shared publication Alyssa S.M. Yong
Michael Smith Laboratories, University of British Columbia, Vancouver V6T 1Z4, Canada
1 shared publication- Amy W. Strilchuk
Michael Smith Laboratories, University of British Columbia, Vancouver V6T 1Z4, Canada
1 shared publication - Bas de Laat
Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands
1 shared publication - Christian J. Kastrup
Department of Biochemistry and Molecular Biology University of British Columbia Vancouver British Columbia Canada
1 shared publication - David Lillicrap
Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON, Canada
1 shared publication
Latest Publications
- 21 February 2024
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 16 (735) , eadh0027
Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A
Antifibrinolytic drugs are used extensively for on-demand treatment of severe acute bleeding. Controlling fibrinolysis may also be an effective strategy to prevent or lessen chronic recurring bleeding in bleeding disorders such as hemophilia A (HA), but current antifibrinolytics have unfavorable pharmacokinetic profiles. Here, we developed a long-lasting antifibrinolytic using small interfering RNA (siRNA) targeting plasminogen packaged in clinically used lipid nanoparticles (LNPs) and tested it to determine whether reducing plasmin activity in animal models of HA could decrease bleeding frequency and severity. Treatment with the siRNA-carrying LNPs reduced circulating plasminogen and suppressed fibrinolysis in wild-type and HA mice and dogs. In HA mice, hemostatic efficacy depended on the injury model; plasminogen knockdown improved hemostasis after a saphenous vein injury but not tail vein transection injury, suggesting that saphenous vein injury is a murine bleeding model sensitive to the contribution of fibrinolysis. In dogs with HA, LNPs carrying siRNA targeting plasminogen were as effective at stabilizing clots as tranexamic acid, a clinical antifibrinolytic, and in a pilot study of two dogs with HA, the incidence of spontaneous or excess bleeding was reduced during 4 months of prolonged knockdown. Collectively, these data demonstrate that long-acting antifibrinolytic therapy can be achieved and that it provides hemostatic benefit in animal models of HA.
- 21 February 2024
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 16 (735) , eadh0027
Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A
Antifibrinolytic drugs are used extensively for on-demand treatment of severe acute bleeding. Controlling fibrinolysis may also be an effective strategy to prevent or lessen chronic recurring bleeding in bleeding disorders such as hemophilia A (HA), but current antifibrinolytics have unfavorable pharmacokinetic profiles. Here, we developed a long-lasting antifibrinolytic using small interfering RNA (siRNA) targeting plasminogen packaged in clinically used lipid nanoparticles (LNPs) and tested it to determine whether reducing plasmin activity in animal models of HA could decrease bleeding frequency and severity. Treatment with the siRNA-carrying LNPs reduced circulating plasminogen and suppressed fibrinolysis in wild-type and HA mice and dogs. In HA mice, hemostatic efficacy depended on the injury model; plasminogen knockdown improved hemostasis after a saphenous vein injury but not tail vein transection injury, suggesting that saphenous vein injury is a murine bleeding model sensitive to the contribution of fibrinolysis. In dogs with HA, LNPs carrying siRNA targeting plasminogen were as effective at stabilizing clots as tranexamic acid, a clinical antifibrinolytic, and in a pilot study of two dogs with HA, the incidence of spontaneous or excess bleeding was reduced during 4 months of prolonged knockdown. Collectively, these data demonstrate that long-acting antifibrinolytic therapy can be achieved and that it provides hemostatic benefit in animal models of HA.