Small interfering RNA (siRNA) holds potential as a therapeutic approach to silence targeted
gene of disease, but siRNA has limited stability in vivo. Therefore, delivery system of siRNA is the key to
siRNA therapeutic application. We attempted to develop a delivery system, which enables siRNA to
demonstrate high stability and long blood circulation. We synthesized a series of bottlebrush-type
copolymers (BBCs) possessing polycationic backbone (less than 30 wt%) and abundant water-soluble side
chains (more than 70 wt%) as siRNA carrier. A siRNA complexed with the BBC was resistant to
nuclease and stable in plasma. Especially, the BBC (10 wt% PLL and 90 wt% PEG) having higher
grafting ratio (≈ 90 wt%) of water-soluble side chains showed 100-times enhanced stability of siRNA in
mouse bloodstream in vivo. Surprisingly, even when the BBC and siRNA separately injected into mouse
at 20 min interval, the BBC increased blood half life of the siRNA. These results suggest that the BBC
has higher selectivity in its ionic interaction to siRNA than other anionic substance in blood components.
To our knowledge, this is the first report of siRNA delivery carrier which prolonged blood circulation of
siRNA without resource-consuming preparation process.