title: Therapeutic targeting in the silent era: advances in non-viral siRNA delivery.
abstract: Gene silencing using RNA-interference, first described in mammalian systems almost a decade ago, is revolutionizing therapeutic target validation efforts both in vitro and in vivo. Moreover, the potential for using short interfering RNA (siRNA) as a therapy in its own right is also progressing at a significant pace. However, the widespread use of such approaches is contingent on having appropriate systems to achieve clinically appropriate, safe, and efficient delivery of siRNA. There are many physicochemical and biological barriers to such delivery, and a growing emphasis on the design and characterisation of non-viral technologies that will overcome these barriers and expedite targeted delivery. This review discusses the considerations and challenges associated with use of siRNA-based therapeutics, including stability and off-target effects. Speculation is made on the properties of an ideal delivery system and the non-viral delivery approaches used to date, both in vitro and in vivo, are classified and discussed. Moreover, the ability of cyclodextrin-based delivery vectors to fulfil many of the criteria of an ideal delivery construct is also elaborated.
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Guo
authors.forename: Karen A
authors.initials: KA
authors.lastname: Fisher
authors.forename: Raphael
authors.initials: R
authors.lastname: Darcy
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
authors.forename: Caitriona
authors.initials: C
authors.lastname: O'Driscoll
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000628:therapy; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D034741:RNA, Small Interfering