Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo

F Takeshita, Y Minakuchi, S Nagahara… - Proceedings of the …, 2005 - National Acad Sciences
F Takeshita, Y Minakuchi, S Nagahara, K Honma, H Sasaki, K Hirai, T Teratani…
Proceedings of the National Academy of Sciences, 2005National Acad Sciences
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 iv 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 …
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-α-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-α 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.
National Acad Sciences