Reactive oxygen species-responsive RNA interference.

Area of Science:

• Chemical synthesis
• Nucleic acid chemistry
• Drug delivery

Background:

• Arylboronic acids exhibit oxidative instability, hindering their use in solid-phase nucleic acid synthesis.
• This instability limits the development of novel nucleic acid-based therapeutics.

Purpose of the Study:

• To overcome the oxidative instability of arylboronic acids for nucleic acid synthesis.
• To develop novel siRNA prodrugs activated by reactive oxygen species (ROS) for targeted cancer therapy.

Main Methods:

• Developed a novel method to stabilize arylboronic acids during solid-phase synthesis.
• Synthesized siRNA prodrugs incorporating stabilized arylboronic acid moieties.
• Demonstrated *in vivo* activation of prodrugs by ROS in a cancer cell model.

Main Results:

• Successfully stabilized arylboronic acids for robust nucleic acid synthesis.
• Engineered siRNA prodrugs that release active siRNA specifically in ROS-rich environments.
• Showcased targeted delivery and activation in cancer cells, minimizing off-target effects.

Conclusions:

• The developed method enables the use of arylboronic acids in solid-phase nucleic acid synthesis.
• Novel ROS-activated siRNA prodrugs offer a promising strategy for targeted cancer treatment.
• This approach facilitates the development of next-generation nucleic acid therapeutics.