Correction of bleeding in experimental severe hemophilia A by systemic delivery of factor VIII-encoding mRNA.

Correction of bleeding in experimental severe hemophilia A by systemic delivery of factor VIII-encoding mRNA. Haematologica. 2019 Jul 09;: Authors: Russick J, Delignat S, Milanov P, Christophe O, Boros G, Denis CV, Lenting PJ, Kaveri SV, Lacroix-Desmazes S Abstract The treatment or prevention of bleeding in patients with hemophilia A rely on replacement therapy with different factor VIII containing products or on the use of by-passing agents, i.e., activated prothrombin complex concentrates or recombinant activated factor VII. Emerging approaches include the use of bispecific anti-factor IXa/factor X antibodies, anti-Tissue Factor Pathway Inhibitor antibodies, interfering RNA to antithrombin, APC-specific serpins or gene therapy. The latter strategies however meet with short term clinical experience and potential adverse effects including the absence of tight temporal and spatial control of coagulation or risk for uncontrolled insertional mutagenesis. The systemic delivery of mRNA allows the endogenous production of the corresponding encoded protein. Thus, injection of lipid nanoparticles-formulated erythropoietin-encoding mRNA resulted in increased erythropoiesis in mice and macaques. Here, we demonstrate that a single injection of in vitro transcribed B domain-deleted factor VIII-encoding mRNA to factor VIII-deficient mice allows the endogenous production of pro-coagulant factor VIII. Circulating FVIII:C levels above 5% of normal l...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research