RNA microsponges for efficient gene silencing

Microsponges that act as both carrier and cargo for the delivery of gene-silencing RNA (siRNA) into cells are described online this week in Nature Materials. The work reports that, compared with conventional siRNA delivery vehicles, one thousand times lower concentration of the microsponges achieves the same degree of gene-silencing effect in tumour-carrying mice. siRNA delivery has so far been hampered by carriers that inefficiently encapsulate RNA, and by its degradation prior to cellular uptake. Using RNA-amplification techniques, Paula Hammond and colleagues made very long chains of connected hairpin RNA strands from circular DNA templates. They observed that the chains self-assembled into sponge-like microspheres of pleated crystalline sheets. Because hairpin RNA is cleaved to form siRNA only inside the cell, the hairpin-RNA microsponges function both as a stable cargo and a carrier. To enhance cellular uptake, the authors made the microsponges ten times smaller by coating them with a highly charged polymer. They show that each polymer-coated microsponge delivers over half a million copies of siRNA per cell.