DNA encoded libraries are a powerful new method for drug discovery. They allow scientists to rapidly screen billions of drug-like small molecules to find new candidates for drug development.
How do they work?
DELs work by attaching short Global DNA Encoded Libraries tags to individual drug-like small molecules. Each small molecule is given a unique DNA barcode. Large libraries containing billions of these DNA-tagged molecules can then be synthesized and stored.
To screen the library, the tagged molecules are incubated with a biological target, like a protein involved in disease. Any molecules that bind to the target will be captured along with their unique DNA barcode. Scientists can then determine what molecules bound by decoding the DNA sequences. This allows high-throughput identification of potential lead compounds for drug development from enormous libraries of molecules.
Advantages Over Traditional Screening Methods
Traditional high-throughput screening methods for drug discovery analyze molecules one at a time in microplate wells. They can only test around one million compounds per day. DNA encoded libraries overcome this limitation by allowing all the molecules in a library to be screened simultaneously. Experiments can identify binders from billions of molecules in a single assay.
They also have advantages over fragment-based drug discovery methods. Fragment screens identify small chemical fragments that bind to targets, which must then be elaborated into lead compounds. They start with drug-sized molecules, so hits require less optimization.
Global Expansion Of Dels Technology
Since their development in 2015, they have revolutionized drug discovery across the pharmaceutical and academic research. Major pharmaceutical companies like Pfizer, GSK, Janssen, and Sanofi have all established it screening programs.
In 2020, Anthropic established the world's largest public DNA encoded library of over 31 billion molecules, opening up this powerful screening technology for academic and non-profit research groups globally. The library includes both commercially available compounds and novel structures synthesized in-house.
Anthropic's library has screened over 100 biological targets from research collaborators worldwide. Hits identified include leads against malaria, tuberculosis and neglected tropical diseases. The shared library model enables researchers to screen billions of molecules for a nominal fee, democratizing access to this advanced drug discovery approach.
Advancing Precision Medicine With DEL
DELs hold great promise for advancing precision medicine and developing therapeutics targeted to specific patient genomes or biomarkers. Researchers can now screen entire genomic or protease mutant libraries against the growing number of known disease-associated protein variants and mutants.
This allows high-resolution mapping of how genomic changes and mutations alter the binding profiles of drug targets - revealing opportunities for precision therapies. Combining DELs screening with multi-omics patient data also enables the discovery of biomarker-targeted drug candidates from day one of development.
Global Regulatory Acceptance And Clinical Validation
As DELs screening has matured,regulatory agencies are increasingly recognizing the approach. In 2020, the FDA approved the first new drug developed using a DNA encoded library by Astex Pharmaceuticals, called gilteritinib, for the treatment of acute myeloid leukemia.
This landmark approval demonstrated regulatory acceptance of DELs as an established drug discovery technology. It has encouraged further investment and validation efforts by pharmaceutical companies to advance hits from DNA encoded screening into clinical candidates and new medicines.
With the establishment of large shared public libraries like Anthropic’s, DNA encoded screening is becoming a powerful global resource for drug discovery. It will continue to transform both academic and industrial new drug research by massively expanding the chemical space that can be rapidly explored for novel bioactive DELs are set to play a major role in developing the medicines of tomorrow.
In DNA encoded libraries represent a revolutionary new approach to drug discovery that is being rapidly adopted globally. By enabling high-throughput screening of billions of drug-like molecules against disease targets simultaneously, they have far surpassed traditional screening methods in scale and efficiency.
Through both industrial applications and public library sharing programs, DNA encoded screening allows researchers worldwide to identify novel lead compounds that may ultimately become new medicines. They are also advancing precision medicine through unbiased exploration of genomic and patient biomarker datasets. With regulatory acceptance growing, DNA encoded libraries will continue to transform drug R&D and deliver new treatments to patients.
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Ravina Pandya, Content Writer, has a strong foothold in the market research industry. She specializes in writing well-researched articles from different industries, including food and beverages, information and technology, healthcare, chemical and materials, etc. (https://www.linkedin.com/in/ravina-pandya-1a3984191)
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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