digilib@itb.ac.id +62 812 2508 8800

In this work, we report a component-minimalspherical nucleic acid (SNA) from monodisperse DNA?polymer conjugates that can load and release nucleic acidtherapeutics in a stimuli-responsive manner. We show thatthis vehicle assembles from only four strands, and conditionalrelease of its antisense therapeutic cargo can be induced uponrecognition of specific oligonucleotide triggers via stranddisplacement. The latter (triggers) may be a microRNA thatoffers additional synergistic therapy, in addition to thepreviously shown ability of the SNA to load hydrophobicdrugs. The SNA is easy to prepare, has dynamic character,releases its cargo only upon the presence of both triggers, andcan survive biological conditions while protecting its cargo. The gene silencing potency of the cargo was tested in live cells andshown to be suppressed when loaded in the SNA, and its activity was restored only upon release with the two triggers. Thisvehicle has the essential characteristics of versatility, ease of synthesis, low cost, highly responsive behavior, and ability tosupport combination therapies, making it a promising candidate for cell-selective drug delivery and clinical transition.