BoneKEy Reports | BoneKEy Watch
Delivery system enables siRNA against Plekho1 to boost bone formation
DOI:10.1038/bonekey.2012.78
Small interference RNA (siRNA) molecules have the potential to treat metabolic bone disorders, but only if they can home in on the osteogenic cells in the bone marrow. In this study, Zhang et al. have developed a delivery system for siRNA that takes it directly to the surfaces at which bone formation occurs.
They attached cationic liposomes to six repeated sequences of aspartate-serine-serine ((AspSerSer)6) and used this to encapsulate an siRNA specific for casein kinase-2 interacting protein-1 encoded by the Plekho1 gene. In vivo studies in rats showed that the siRNA-((AspSerSer)6) complex was able to target osteogenic cells, resulting in a reduction of Plekho1 expression, which resulted in stimulation of osteogenesis.
The study is an important proof of concept for the delivery system and it also confirms that targeting Plekho1 using a specific siRNA can increase bone formation in normal and osteoporotic rats. Treated animals in both groups showed an increase in bone mass and an enhancement of bone micro-architecture.
Editor's comment: Employing siRNA against Plekho1, a negative regulator of bone formation is a novel approach to stimulating bone formation. The siRNA-containing liposome is linked to an (AspSerSer)6 oligopeptide to target bone formation surfaces. The RNAi targeting strategy may have therapeutic potential in metabolic bone disease and osteoporosis.
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