title: In Vivo siRNA Delivery Using JC Virus-like Particles Decreases the Expression of RANKL in Rats.
abstract: Bone remodeling requires a precise balance between formation and resorption. This complex process involves numerous factors that orchestrate a multitude of biochemical events. Among these factors are hormones, growth factors, vitamins, cytokines, and, most notably, osteoprotegerin (OPG) and the receptor activator for nuclear factor-kappaB ligand (RANKL). Inflammatory cytokines play a major role in shifting the RANKL/OPG balance toward excessive RANKL, resulting in osteoclastogenesis, which in turn initiates bone resorption, which is frequently associated with osteoporosis. Rebalancing RANKL/OPG levels may be achieved through either upregulation of OPG or through transient silencing of RANKL by means of RNA interference. Here, we describe the utilization of a viral capsid-based delivery system for in vivo and in vitro RNAi using synthetic small interfering RNA (siRNA) molecules in rat osteoblasts. Polyoma JC virus-derived virus-like particles are capable of delivering siRNAs to target RANKL in osteoblast cells both in vitro and in a rat in vivo system. Expression levels were monitored using quantitative real-time polymerase reaction and enzyme-linked immunosorbent assay after single and repeated injections over a 14-day period. Our data indicate that this is an efficient and safe route for in vivo delivery of gene modulatory tools to study important molecular factors in a rat osteoporosis model.
authors.affiliation: Department of Trauma Surgery and Reconstructive Surgery, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Hoffmann
authors.affiliation: Primate Genetics Laboratory, Junior Research Group "Medical RNA Biology," German Primate Center, Göttingen, Germany.
authors.forename: Kai O
authors.initials: KO
authors.lastname: Böker
authors.affiliation: Primate Genetics Laboratory, Junior Research Group "Medical RNA Biology," German Primate Center, Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Primate Genetics Laboratory, Junior Research Group "Medical RNA Biology," German Primate Center, Göttingen, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Eckermann-Felkl
authors.affiliation: Primate Genetics Laboratory, Junior Research Group "Medical RNA Biology," German Primate Center, Göttingen, Germany.
authors.forename: Angelina
authors.initials: A
authors.lastname: Schuder
authors.affiliation: Department of Trauma Surgery and Reconstructive Surgery, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Komrakova
authors.affiliation: Department of Trauma Surgery and Reconstructive Surgery, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Sehmisch
authors.affiliation: Primate Genetics Laboratory, Junior Research Group "Medical RNA Biology," German Primate Center, Göttingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Gruber