RT Journal Article
T1 Development and characterization of a factor V‐deficient CRISPR cell model for the correction of mutations
A1 Serrano Ramos, Luis Javier
A1 García Arranz, Mariano
A1 De Pablo Moreno, Juan Andrés
A1 Segovia, José Carlos
A1 Olivera Salazar, Rocío
A1 García Olmo, Damián
A1 Liras Martín, Antonio
AB 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.
PB MDPI
SN 1661-6596
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/110863
UL https://hdl.handle.net/20.500.14352/110863
LA eng
NO Serrano, L. J., Garcia‐arranz, M., De Pablo‐Moreno, J. A., Segovia, J. C., Olivera‐salazar, R., Garcia‐olmo, D., & Liras, A. (2022). Development and Characterization of a Factor V‐Deficient CRISPR Cell Model for the Correction of Mutations. International Journal of Molecular Sciences, 23(10). https://doi.org/10.3390/IJMS23105802
NO This study was supported by the following public grants: Health Research, Instituto de Salud Carlos III; European Regional Development (RETICS RD 16/0011/00011 and RD 16/0011/0013); Directorate General for Research of the Community of Madrid (AvanCell-CM; Ref. S2017/BMD-3692); State Research Agency (PID2020-119637RB-I00). It also received funds from the Association for the Research and Cure of Factor V Deficiency (ASDEFAV).
NO European Commission
NO Ministerio de Ciencia e Innovación (España)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III
NO Asociación para la Investigación y Cura del Déficit del Factor V
DS Docta Complutense
RD 8 abr 2025