Aptamer technology is an exciting new field that is rapidly expanding our understanding of how nucleic acid molecules can regulate biological systems. The ability to engineer DNA and RNA ligands that selectively bind to target molecules holds tremendous promise across numerous industries from healthcare to environmental remediation. In this article, we explore what aptamers are, how they are discovered through a process known as SELEX, and highlight some of their most promising applications.
What are Aptamers?
Aptamers are short, single-stranded DNA or RNA oligonucleotides that bind to a specific target molecule such as proteins, peptides, toxins, or even entire organisms like bacteria or viruses. The word "aptamer" is derived from the Latin "aptus" meaning to fit or adapt and were originally referred to as chemical antibodies. Much like antibodies produced by the immune system, aptamers recognize their targets with high affinity and selectivity, making them excellent molecular recognition agents. Their small size of around 15 nucleotides enables them to access targets in complex environments that antibodies may not be able to reach.
Discovery Through SELEX
The systematic evolution of ligands by exponential enrichment (SELEX) process is used to identify aptamers that bind to a desired target. SELEX involves repeatedly selecting nucleic acid sequences from a random library of around 1014-1015 unique oligos that are able to bind the target molecule. Unbound sequences are washed away while the bound sequences are amplified by PCR and used as the input for the next selection round. Through 10-15 rounds of selection and amplification, the pool becomes enriched for the sequences that bind tightest. High-throughput sequencing is then used to identify the exact sequences of the aptamers selected through SELEX.
Medical Applications
Due to their high affinity and specificity, Aptamers hold tremendous potential as therapeutic and diagnostic agents. Aptamers can be engineered to bind disease-related proteins and intracellular targets, allowing them to potentially act as anticoagulants, antivirals, antineoplastics, and more. One such aptamer known as Macugen gained FDA approval in 2004 for the treatment of wet age-related macular degeneration, the leading cause of blindness. Other aptamers are in clinical trials for conditions like monoclonal gammopathy, coagulation disorders, and cancer. Their small size also enables them to be readily cleared from the body, making them safer than monoclonal antibodies. Looking ahead, these nucleic acid recognition elements are positioned to transform the way we treat and diagnose disease.
Environmental and Food Applications
Outside of medicine, aptamers show promise for environmental monitoring and food safety applications as well. By developing aptamers that bind pollutants, toxins, and pathogenic microbes, they could serve as recognition components in biosensors for real-time detection. One aptamer was shown to selectively bind the mycotoxin patulin produced by certain molds, allowing detection down to parts-per-billion levels directly in apple juice. In wastewater treatment, aptamers may help remove or detect heavy metals, endocrine disruptors, and more. Their thermal stability also makes them well-suited for monitoring throughout industrial food processing as an alternative to antibodies currently used. Further optimization is still needed but aptamers could fill critical roles in environmental remediation and ensuring a safe, sustainable food supply.
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