Delivery of MicroRNAs by plant virus-based nanoparticles to functionally alter the osteogenic differentiation of human mesenchymal stem cells

MicroRNA-26a (miR-26a) has been verified to promote osteogenic differentiation of mesenchymal stem cells in recent years. The main obstacles to its application in bone regeneration are instability in the physiological environment and low efficiency of cellular membrane penetration. To overcome these prob-lems, we constructed a novel plant virus gene delivery system based on Cowpea chlorotic mottle virus (CCMV). By encapsulating miR-26a with purified capsid protein (CP) dimers derived from CCMV, CP-miR-26a (CP26a) virus-like particles (VLPs) were obtained. CP26a retained a structure similar to the na-tive CCMV and protected miR-26a from digestion with its exterior CP. Moreover, CP26a featured simi-lar cellular uptake efficiency, osteogenesis promotion ability, and better biocompatibility compared with Lipofectamine20 0 0-miR-26a (lipo26a), which indicated a promising prospect for CCMV as a novel gene delivery system.(c) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.