title: Optimized DNA "Nanosuitcases" for Encapsulation and Conditional Release of siRNA.
abstract: We set out to design, synthesize, and optimize a DNA-minimal cage capable of encapsulating oligonucleotide drugs to facilitate their delivery. Through rational design and optimization using in vitro assays, we have assembled the first DNA "nanosuitcase" that can encapsulate a siRNA construct and release it upon recognition of an oligonucleotide trigger. The latter may be a mRNA or a microRNA (miRNA) which offers potential for dual or synergistic therapy. This construct assembles in near 100% yield, releases its cargo on demand, and can sustain biological conditions. Moreover, we find that the DNA scaffold is able to protect its cargo against site-specific cleavage and nuclease degradation. Release of the cargo is performed with fixed cells using a FRET-enabled construct imaged by confocal microscopy and reveals that the DNA cage remains responsive at the molecular level in a complex cellular environment. We foresee this construct will be able to address challenges in drug delivery, more specifically in nontoxic delivery and targeted release.
authors.affiliation: Department of Chemistry, McGill University, and Center for Self-Assembled Chemical Structures, 801 Sherbrooke Street West, Montréal, Québec, Canada H3A 0B8.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Bujold
authors.affiliation: Department of Chemistry, McGill University, and Center for Self-Assembled Chemical Structures, 801 Sherbrooke Street West, Montréal, Québec, Canada H3A 0B8.
authors.forename: John C C
authors.initials: JCC
authors.lastname: Hsu
authors.affiliation: Department of Chemistry, McGill University, and Center for Self-Assembled Chemical Structures, 801 Sherbrooke Street West, Montréal, Québec, Canada H3A 0B8.
authors.forename: Hanadi F
authors.initials: HF
authors.lastname: Sleiman