Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Banco de datos
Tipo de estudio
Tipo del documento
Revista
País de afiliación
Intervalo de año de publicación
1.
Nature ; 593(7859): 429-434, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-34012082

RESUMEN

Gene-editing technologies, which include the CRISPR-Cas nucleases1-3 and CRISPR base editors4,5, have the potential to permanently modify disease-causing genes in patients6. The demonstration of durable editing in target organs of nonhuman primates is a key step before in vivo administration of gene editors to patients in clinical trials. Here we demonstrate that CRISPR base editors that are delivered in vivo using lipid nanoparticles can efficiently and precisely modify disease-related genes in living cynomolgus monkeys (Macaca fascicularis). We observed a near-complete knockdown of PCSK9 in the liver after a single infusion of lipid nanoparticles, with concomitant reductions in blood levels of PCSK9 and low-density lipoprotein cholesterol of approximately 90% and about 60%, respectively; all of these changes remained stable for at least 8 months after a single-dose treatment. In addition to supporting a 'once-and-done' approach to the reduction of low-density lipoprotein cholesterol and the treatment of atherosclerotic cardiovascular disease (the leading cause of death worldwide7), our results provide a proof-of-concept for how CRISPR base editors can be productively applied to make precise single-nucleotide changes in therapeutic target genes in the liver, and potentially in other organs.


Asunto(s)
Sistemas CRISPR-Cas , LDL-Colesterol/sangre , Edición Génica , Modelos Animales , Proproteína Convertasa 9/genética , Adenina/metabolismo , Animales , Células Cultivadas , Femenino , Hepatocitos/metabolismo , Humanos , Hígado/enzimología , Mutación con Pérdida de Función , Macaca fascicularis/sangre , Macaca fascicularis/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Mutagénesis Sitio-Dirigida , Proproteína Convertasa 9/sangre , Proproteína Convertasa 9/metabolismo , Factores de Tiempo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA