Circular L-RNA aptamer promotes target recognition and controls gene activity

Area of Science:

• Biochemistry and Molecular Biology
• Nucleic Acid Chemistry
• Synthetic Biology

Background:

• Aptamers, particularly Spiegelmers (L-RNA aptamers) composed of unnatural nucleotides, offer expanded functional complexity.
• Current L-RNA aptamer applications and target binding properties require enhancement for broader utility.
• Rational design of aptamers with unnatural nucleotides and chemical moieties is key to advancing their capabilities.

Purpose of the Study:

• To develop a method for generating circular L-RNA aptamers.
• To enhance the binding affinity and selectivity of L-RNA aptamers.
• To explore novel applications of circular L-RNA aptamers in biological systems.

Main Methods:

• Development of a robust strategy for quantitative generation of circular L-RNA aptamers.
• Characterization of the binding properties of the novel circular L-RNA aptamer (cycL-Apt.4-1c).
• Demonstration of applications in controlling RNA-protein interactions and gene activity.

Main Results:

• Successfully generated the first circular L-RNA aptamer, cycL-Apt.4-1c.
• Demonstrated substantially enhanced binding affinity and selectivity towards its target compared to linear counterparts.
• Reported novel applications in modulating RNA-protein interactions, telomerase activity, and gene expression.

Conclusions:

• The developed strategy provides a simple and robust method for creating circular L-RNA aptamers.
• Circular L-RNA aptamers exhibit improved target binding characteristics.
• This work opens new avenues for diverse applications of L-RNA aptamers in biotechnology and medicine.