Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo.
Proc Natl Acad Sci U S A
; 102(34): 12177-82, 2005 Aug 23.
Article
en En
| MEDLINE
| ID: mdl-16091473
ABSTRACT
Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery for siRNAs toward treatment of bone-metastatic cancer. Accordingly, we report here that i.v. injection of GL3 luciferase siRNA complexed with atelocollagen showed effective reduction of luciferase expression from bone-metastatic prostate tumor cells developed in mouse thorax, jaws, and/or legs. We also show that the siRNA/atelocollagen complex can be efficiently delivered to tumors 24 h after injection and can exist intact at least for 3 days. Furthermore, atelocollagen-mediated systemic administration of siRNAs such as enhancer of zeste homolog 2 and phosphoinositide 3'-hydroxykinase p110-alpha-subunit, which were selected as candidate targets for inhibition of bone metastasis, resulted in an efficient inhibition of metastatic tumor growth in bone tissues. In addition, upregulation of serum IL-12 and IFN-alpha levels was not associated with the in vivo administration of the siRNA/atelocollagen complex. Thus, for treatment of bone metastasis of prostate cancer, an atelocollagen-mediated systemic delivery method could be a reliable and safe approach to the achievement of maximal function of siRNA.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Neoplasias Óseas
/
Terapia Genética
/
Regulación Neoplásica de la Expresión Génica
/
Colágeno
/
ARN Interferente Pequeño
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2005
Tipo del documento:
Article
País de afiliación:
Japón