Preclinical safety and bleeding evaluation in swine for a small interfering RNA-lipid nanoparticle that prevents excess fibrinogen synthesis.

ABSTRACT:

Background

Fibrinogen levels can drastically increase from inflammation, trauma, or surgery, which increases risk of venous thromboembolism (VTE). We developed small interfering RNA (siFibrinogen) that decreased fibrinogen production and thrombosis in rodent models, which became effective hours after administration and knockdown lasted over a week. Here, we tested whether knockdown of fibrinogen was feasible and safe in a preclinical large animal model. We hypothesized that fibrinogen could be controllably knocked down to levels that still enable hemostasis and avoid limitations of the current standard of care agent, low-molecular-weight heparin (LMWH).

Objectives

This study evaluated the preclinical safety and feasibility of a novel therapy for VTE prophylaxis for complicat

SUBMITTER: Seadler MS 

PROVIDER: S-EPMC12766900 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature