Selection and characterization of human PCSK9 antibody from phage displayed antibody library.
Biochem Biophys Res Commun
; 463(4): 712-8, 2015 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-26056005
ABSTRACT
Proprotein convertase subtilisin/kexin type 9 (PCSK9), which involves in low-density lipoprotein cholesterol (LDL-C) metabolism by interacting with the LDL receptor, is considered as a potent therapeutic target for treating hypercholesterolemia. Here, a fab antibody phage display library was constructed and employed for bio-panning against recombinant PCSK9. A Fab fragment (designated PA4) bound with high affinity to PCSK9 was isolated after four rounds of panning. The fully human antibody IgG1-PA4 bound specifically to PCSK9 with nanomolar affinity. In vitro, IgG1-PA4 inhibited PCSK9 binding to LDLR and attenuated PCSK9-mediated degradation of LDLR on the HepG2 cell surface. In C57BL/6 mice, administration of IgG1-PA4 at 30 mg/kg increased hepatic LDLR protein levels by as much as 3 fold when compared with control. Taken together, these results suggested that the IgG1-PA4 can be served as a potential candidate for the treatment of hypercholesterolemia by inhibiting PCSK9-mediated degradation of cell surface LDLRs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bacteriófagos
/
Serina Endopeptidases
/
Pró-Proteína Convertases
/
Anticorpos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article