Thermo-Responsive Polymer-siRNA Conjugates Enabling Artificial Control of Gene Silencing around Body Temperature

Area of Science:

• Biotechnology
• Materials Science
• Molecular Biology

Background:

• Controlling small interfering RNA (siRNA) activity with external stimuli enables targeted therapeutic effects.
• Thermo-responsive systems offer potential for localized therapeutic interventions near body temperature.

Purpose of the Study:

• To develop a technology for controlling siRNA activity in a thermo-responsive manner.
• To enable siRNA activity control at temperatures close to physiological conditions.

Main Methods:

• siRNA was conjugated with a thermo-responsive copolymer of N-isopropylacrylamide (NIPAAm) and N,N-dimethylacrylamide (DMAA).
• The copolymer's composition was optimized for a lower critical solution temperature (LCST) around body temperature.
• Cellular uptake and gene silencing efficiency of the conjugates were evaluated at different temperatures.

Main Results:

• The siRNA-copolymer conjugate exhibited a coil-to-globule transition above its LCST of 38.0°C.
• Hydrodynamic diameter changed from ~11.5 nm at 37°C to ~9.8 nm at 41°C.
• Cellular uptake and gene silencing efficiency increased significantly from 37°C to 41°C.

Conclusions:

• siRNA activity can be precisely controlled thermo-responsively by tuning copolymer LCST near body temperature.
• This technique provides a promising strategy for selective siRNA-mediated therapeutic effects in vivo.