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5 exciting uses for DNA aptamers on DNA Day!


DNA Day 2024 logo long

April 25th is DNA Day and we’re celebrating DNA aptamers and the innovation they are bringing from new medicines to new life science reagents.

This day was set up to commemorate the discovery of the double helix and the completion of the Human Genome Project—two key breakthroughs that paved the way for advances in genome engineering.

Advances range from rapid whole genome sequencing to CRISPR-Cas9 gene editing and modifying microbes as a new fuel source. But did you know that small pieces of single-stranded DNA have a unique function as aptamers? And that DNA aptamers are providing unique solutions from basic research to new treatments?

What is a DNA aptamer?

Aptamers are short sequences of single-stranded DNA. Based on their sequence they fold into unique conformations that can selectively bind to a specific target, including proteins, peptides, carbohydrates, small molecules, toxins, and even live cells. DNA is highly stable (think of DNA extraction from woolly mammoths after 1.2 million years) and cheap to manufacture with high consistency. Consequently, DNA aptamers are often used as research reagents and affinity tools in early discovery, diagnostics and as new therapeutic modalities.

At Aptamer Group, we use both DNA and RNA libraries to deliver the best binder for your specific project, so we are pleased to celebrate DNA day and the contribution that DNA-based aptamers have made to science by highlighting a few of our favourite innovations so far.

DNA aptamer diagnostics for early detection of Alzheimer’s disease

Our current partnership with Neuro-Bio is seeking to develop a lateral flow test for Alzheimer’s disease. Based on a new biomarker, we are developing a matched pair of DNA aptamers that can be used in a rapid diagnostic assay for the early detection of this neurodegenerative disease.

The novel Alzheimer’s disease biomarker, a peptide ‘T14’was discovered and is currently being further validated by Neuro-Bio, led by the eminent neuroscientist Baroness Susan Greenfield. Early detection of Alzheimer’s disease is critical to allow interventions that could prevent the onset of devastating memory loss and confusion in these patients.

The high stability and consistent manufacture of DNA aptamers makes them ideal for diagnostic use for simple global logistics, while the in vitro development of these reagents means we can prevent the need for animal-derived antibodies in its diagnostic.

Beacons for new shining lights in small molecule analysis

Small molecules are ubiquitous, from drugs, such as chemotherapeutics and antibiotics, to food additives, such as vitamin supplements or environmental contaminants. Detecting and monitoring these molecules is vital for many processes but can be slow and costly with traditional methods like mass spectrometry.

DNA aptamers can be used as beacons for convenient analysis of small molecule analytes through high selectivity affinity-based assays. These reagents are fluorescent FRET-based single reagents for small molecule detection and concentration analysis in solution. 

In this application the flexible backbone of the DNA aptamer allows movement in target binding and release for FRET readouts. They can be developed directly as reporter molecules or engineered from current DNA aptamers to allow use in orthogonal assays. Our recent poster, Optimer binders for the detection and analysis of folate metabolites, shows how these have been developed for multiple species in the metabolic pathway of folate vitamins, for highly specific concentration-dependent responses, with high reproducibility and assay stability over time.  

DNA aptamer therapies

world DNA day aptamer

DNA aptamers were not initially explored as therapeutic molecules. Instead, RNA aptamers were preferred as they are more amenable to modification for longer half-lives. However, of the nine current aptamers in clinical trial, two are unmodified DNA molecules.

Aptoll is a DNA aptamer therapy in phase II trials for acute ischaemic stroke and phase I trials for long COVID. This aptamer is a Toll-like receptor 4 antagonist. In cases of ischaemic stroke it acts to inhibit inflammation, reduce infarct volumes and improve functional outcomes. Trials with Aptoll have shown excellent safety profiles, and when used within 6 hours of stroke onset in combination with endovascular treatment showed reduced mortality and disability at 90 days.

BC007 is a second DNA aptamer therapy that is currently in phase II trials for heart failure . This DNA aptamer neutralises functionally active, pathological auto-antibodies directed against G protein-coupled receptors. Pathological versions of these auto-antibodies have been found to function in pulmonary hypertension, glaucoma, Chronic Fatigue Syndrome (CFS), long COVID and heart failure. BC007 binds to and eliminates auto-antibodies against the beta-1-adrenoceptor that regulates heart rate and contraction strength. Ongoing trials with this DNA aptamer have shown good patient tolerability and efficacy for heart failure.

Taking the heat out of hot-starts

World DNA Day hot start PCR

DNA polymerases used in PCR reactions can add bases to ssDNA in a non-template-dependent manner. At the high temperatures used during PCR thermal cycling, this activity is reduced, and annealing becomes more stringent. Yet, at lower temperatures, including room temperature, this activity can impact the reaction specificity, leading to inaccurate results. Preventing the low-temperature activity and retaining the reaction specificity is crucial to the experiment.

‘Hot-start’ PCR offers a way to overcome the specificity issues. NEB, the life science reagent supplier, now offers a best in class temperature-sensitive polymerase inhibitor that is based on DNA aptamers. The aptamer used by NEB inhibits enzyme activity at room temperature and is proven to yield highly specific PCR reactions with advantages including:

  • The aptamer inhibition/activation process is fully reversible, preventing any further polymerase activity at the end of thermal cycling.
  • The aptamer inhibition is released at ~45°C), removing the need for high temperature activation steps and enabling faster protocols.

Building on DNA aptamers for better binders

After working with DNA aptamers at Aptamer Group for over a decade, we have built on our standard development process. Optimer+ is a novel affinity ligand platform that can be considered amongst the next generation of binding reagents.

Optimer+ uses a modified DNA library that creates hybrid DNA-peptide binders engineered with a scaffold structure that bridge the gap between traditional aptamers and protein-based affinity ligands. The latest proof-of-concept results show that the Optimer+ platform can produce highly specific binders with significantly higher affinity than the current technology platform. Development times for Optimer+ are also significantly faster than existing aptamer-based approaches.  Lab-based results have shown Optimer+ binders appear stable in blood serum and are not harmful to cells. Furthermore, preliminary experiments in mice have shown Optimer+ binders to be well tolerated demonstrating the basic requirements for therapeutic applications. 

From deciphering the structure of double-stranded DNA to cracking the human genome, over the past 70 years our understanding of DNA has advanced hugely. We are now engineering DNA molecules to offer better research reagents, improved diagnostics and novel therapeutic approaches using aptamer technology.

If you’d like to talk to the team to see how aptamers could support your research get in touch today.

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