Recent Progress and Opportunities for Nucleic Acid Aptamers.

Area of Science:

• Biochemistry
• Molecular Biology
• Biotechnology

Background:

• Aptamers are nucleic acid ligands with high-affinity binding capabilities, emerging from studies on viral protein modulation.
• They offer advantages over antibodies, including small size, flexibility, good biocompatibility, and low immunogenicity.
• The first aptamer drug, Macugen, was approved in 2004, highlighting therapeutic potential.

Purpose of the Study:

• To review the challenges and opportunities in aptamer development and application.
• To highlight recent progress in aptamer technology and systematic evolution of ligands by exponential enrichment (SELEX).
• To discuss the renewed interest in aptamers for diagnostics and therapeutics, especially in the context of COVID-19.

Main Methods:

• Aptamers are isolated using in vitro selection (SELEX) from randomized oligonucleotide libraries.
• The review analyzes challenges related to aptamer binding performance and reproducibility.
• Conformational dynamics and binding under varying conditions are crucial areas for investigation.

Main Results:

• Despite initial promise and FDA approval of Macugen, many aptamers have faced challenges in human clinical trials regarding safety and efficacy.
• Novel technologies and advances in aptamer design and SELEX are driving progress in the field.
• Aptamers are gaining renewed interest due to their unique properties, particularly relevant in the current era.

Conclusions:

• Aptamers possess significant therapeutic and diagnostic potential, but clinical translation requires overcoming hurdles in binding performance and reproducibility.
• Continued research into aptamer conformational dynamics and binding characteristics is essential.
• Recent technological advancements offer renewed optimism for the successful clinical application of aptamers.