Abstract
Small interfering RNAs (siRNA) have enormous potential as therapeutics to target and treat various bone disorders such as osteoporosis and cancer bone metastases. However, effective and specific delivery of siRNA therapeutics to bone and bone-specific cells in vivo is very challenging. To realize the full therapeutic potential of siRNA in treating bone disorders, a safe and efficient, tissue- and cell-specific delivery system must be developed. This review focuses on recent advances in bone site-specific delivery of siRNA at the tissue or cellular level. Bone-targeted nanoparticulate siRNA carriers and various bone-targeted moieties such as bisphosphonates, oligopeptides (Asp)8 and (AspSerSer)6, and aptamers are highlighted. Incorporation of these bone-seeking targeting moieties into siRNA carriers allows for recognition of different sub-tissue functional domains of bone and also specific cell types residing in bone tissue. It also provides a means for bone-formation surface-, bone-resorption surface-, or osteoblast-specific targeting and transportation of siRNA therapeutics. The discussion mainly focuses on systemic and local bone-specific delivery of siRNA in osteoporosis and bone metastasis preclinical models.
Highlights
Bone is a mineralized connective tissue that functions as a structural framework for the body
This review focuses on recent advances in improv ing bone-specific delivery of RNA interference (RNAi) at a tissue or cellu lar level
This review focuses on these bonetargeted molecules and carrier systems in the preclinical models of osteoporosis and bone metastasis
Summary
Bone is a mineralized connective tissue that functions as a structural framework for the body. Both the systemic and local delivery of bone targeted RNAi therapeutics in two kinds of bone disorders - osteoporosis and bone metastasis are described. The atelocollagen-mediated delivery system was used to target siRNA to bone-metastatic lesions to silence endogenous genes involved in skeletal metastasis of prostate cancer[28].
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