%0 Journal Article
%A Serrano Ramos, Luis Javier
%A García Arranz, Mariano
%A De Pablo Moreno, Juan Andrés
%A Segovia, José Carlos
%A Olivera Salazar, Rocío
%A García Olmo, Damián
%A Liras Martín, Antonio
%T Development and characterization of a factor V‐deficient CRISPR cell model for the correction of mutations
%D 2022
%@ 1661-6596
%U https://hdl.handle.net/20.500.14352/110863
%X Factor V deficiency, an ultra-rare congenital coagulopathy, is characterized by bleeding episodes that may be more or less intense as a function of the levels of coagulation factor activity present in plasma. Fresh-frozen plasma, often used to treat patients with factor V deficiency, is a scarcely effective palliative therapy with no specificity to the disease. CRISPR/Cas9-mediated gene editing, following precise deletion by non-homologous end-joining, has proven to be highly effective for modeling on a HepG2 cell line a mutation similar to the one detected in the factor V-deficient patient analyzed in this study, thus simulating the pathological phenotype. Additional CRISPR/Cas9-driven non-homologous end-joining precision deletion steps allowed correction of 41% of the factor V gene mutated cells, giving rise to a newly developed functional protein. Taking into account the plasma concentrations corresponding to the different levels of severity of factor V deficiency, it may be argued that the correction achieved in this study could, in ideal conditions, be sufficient to turn a severe phenotype into a mild or asymptomatic one.
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