Targeted RNA Degradation via LipoSM-RiboTAC Nanoparticles: A Versatile Platform for Cancer Therapy

Area of Science:

• Biochemistry
• Molecular Biology
• Therapeutics

Background:

• RNA molecules are crucial in disease pathogenesis, regulating gene expression.
• RNA-targeted therapeutics represent a significant advancement in precision medicine.
• Ribonuclease-targeting chimeras (RiboTACs) utilize endogenous RNases for RNA degradation, offering therapeutic advantages.

Purpose of the Study:

• To develop a novel, efficient, and low-toxicity platform for targeted RNA degradation in cancer therapy.
• To overcome limitations of conventional RiboTAC development, such as complex screening and structural challenges.

Main Methods:

• Proposed a split-and-mix-RiboTAC (LipoSM-RiboTAC) system based on liposome self-assembly.
• Evaluated the platform's cellular internalization, RNase L activation, and oncogenic RNA degradation capabilities.

Main Results:

• LipoSM-RiboTAC demonstrated facile screening through self-optimized biomolecule spatial recognition.
• The platform exhibited rapid cellular uptake and robust activation of endogenous RNase L.
• Achieved precise degradation of oncogenic RNAs, indicating therapeutic potential.

Conclusions:

• Established an efficient and low-toxicity platform for targeted RNA degradation using LipoSM-RiboTAC.
• The developed platform shows promise for cancer therapy and advances precision gene therapy strategies.