title: Self-assembled RNA interference microsponges for efficient siRNA delivery.
abstract: The encapsulation and delivery of short interfering RNA (siRNA) has been realized using lipid nanoparticles, cationic complexes, inorganic nanoparticles, RNA nanoparticles and dendrimers. Still, the instability of RNA and the relatively ineffectual encapsulation process of siRNA remain critical issues towards the clinical translation of RNA as a therapeutic. Here we report the synthesis of a delivery vehicle that combines carrier and cargo: RNA interference (RNAi) polymers that self-assemble into nanoscale pleated sheets of hairpin RNA, which in turn form sponge-like microspheres. The RNAi-microsponges consist entirely of cleavable RNA strands, and are processed by the cell's RNA machinery to convert the stable hairpin RNA to siRNA only after cellular uptake, thus inherently providing protection for siRNA during delivery and transport to the cytoplasm. More than half a million copies of siRNA can be delivered to a cell with the uptake of a single RNAi-microsponge. The approach could lead to novel therapeutic routes for siRNA delivery.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Jong Bum
authors.initials: JB
authors.lastname: Lee
authors.forename: Jinkee
authors.initials: J
authors.lastname: Hong
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Bonner
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Poon
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000818:Animals; D001692:Biological Transport; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D034622:RNA Interference; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D034741:RNA, Small Interfering