Functional Aptamers In Vitro Evolution for Intranuclear Blockage of RNA-Protein Interaction

Area of Science:

• Biotechnology
• Molecular Biology
• Drug Discovery

Background:

• Aptamer-based drug development has faced challenges due to lengthy selection processes and pharmacokinetic limitations.
• Traditional methods require separate steps for affinity acquisition and functional screening, hindering efficiency.
• Postselection modifications are often needed to improve aptamer performance, adding complexity.

Purpose of the Study:

• To introduce a novel in vitro screening platform, Functional Aptamers in vitro Evolution (FAIVE), for rapid generation of functional aptamers.
• To integrate affinity acquisition, functional screening, and chemical diversity into a single process.
• To accelerate the development of aptamer-based therapeutics targeting intracellular functions.

Main Methods:

• The FAIVE platform integrates aptamer selection with functional screening and chemical diversity.
• Demonstrated application targeting HIV-1 Tat protein and TAR RNA interactions.
• Explored lipid nanoparticle delivery systems for enhanced intracellular delivery.

Main Results:

• FAIVE successfully generated functional aptamers with significant intracellular blocking effects.
• The platform demonstrated efficiency in targeting intranuclear RNA-protein interactions.
• Lipid nanoparticle delivery enhanced the intracellular targeting potential of aptamers.

Conclusions:

• FAIVE offers a streamlined approach to aptamer discovery and development.
• The platform has the potential to expedite the creation of versatile and effective aptamer-based drugs.
• Enhanced intracellular delivery expands the therapeutic applications of aptamers.