SDSSD peptide modified polyvinylamine − A novel bone-targeting RNA delivery system

Bone-related disorders have become a prevailing concern in older men and postmenopausal women. Traditional methods of treatment, though have benefits, their inability to target specific cells or tissues increases their ineffectiveness and side effects. RNA therapy has emerged as an alternative to conventional therapy owing to its specific targeting ability. However, the lack of appropriate RNA vectors remains a major problem for successful RNA therapy. Here, we designed a delivery system, (SDSSD-PVAm (PS)) based on a cationic polymer, polyvinylamine (PVAm), and a bone-targeting peptide, SDSSD (Serine-Aspartate-Serine-Serine-Aspartate), to deliver a therapeutic RNA, anti-miR-138-5p, to the bone tissue. The results showed that the SDSSD modification not only had no negative effect on the RNA-carrying or protection abilities of PVAm but also improved targeting and RNA delivery to osteoblasts and improve osteogenic potential of the cells by improving the expression of osteogenic genes both at RNA and protein level. Recombinant anti-miR-138-5p delivered through PS was highly enriched in the bone tissue, and the resultant nanoparticles could circulate for a longer time in the blood with negligible toxicity. The results showed that improved RNA delivery through PS significantly increased the rate of bone formation and improved trabecular and cortical bone microarchitecture, resulting in enhanced bone mass in ovariectomy (OVX) and hind limb unloading (HLU) model mice. These results demonstrate that SDSSD-PVAm is a novel RNA delivery system for bone-related disorders, such as osteoporosis.