Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

Academic DNA-Encoded Library Resource

In plain English

AI plain-English summary

A new national facility will offer UK academic researchers free access to DNA-encoded libraries containing up to 10 million drug-like compounds, allowing them to rapidly screen for molecules that bind to their target proteins. Most drug discovery starts with finding a small molecule that sticks to a disease-related protein. Large pharmaceutical companies routinely use DNA-encoded libraries (DELs) for this, but the technology has been largely out of reach for academic labs due to cost and expertise. Each compound in a DEL carries a unique DNA barcode, so after mixing millions of compounds with a target protein, researchers can simply sequence the DNA to identify which ones bound. This is far faster and simpler than traditional high-throughput screening. If successful, the resource will deliver validated hit compounds to more than 20 research groups by 2025, accelerating the translation of novel drug targets from UK labs into early-stage drug candidates. The facility is designed to be sustainable beyond the initial funding period, creating a permanent infrastructure for academic drug discovery. This could shorten the gap between fundamental biological discoveries and the development of new treatments for diseases that currently lack effective therapies.

View original technical description
Our goal is to enhance and accelerate the validation and translation of new drug targets identified by the UK academic biomedical research community. In order to achieve this we will establish a DNA-Encoded Library (DEL) screening resource that will provide cost-free and commitment-free access to high-throughput compound screening for academic research groups, by; 1) Designing and preparing DNA-encoded libraries containing 5-10 million diverse and drug-like compounds, representing a unique resource for academic researchers. 2) Utilising these libraries to undertake 40 target selections against novel protein targets for academic users, delivering validated hit compounds to >20 research groups by 2025. 3) Developing a sustainable and expandable resource which will continue to deliver beyond the current funding period. DELs are an established screening approach that are utilised by the majority of large pharmaceutical companies. The technology allows for the rapid identification of ligands for a target protein with a very simple protocol compared to other screening approaches. Active compounds are identified by affinity selection of protein-binding compounds from libraries containing millions of different compounds that are each linked to a unique DNA sequence. The DNA tag allows for rapid and high-throughput deconvolution of the active compounds by next-generation sequencing.

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Researchers

Andreas Brunschweiger (EPMC Awardee)Leach (EPMC Awardee)Martin Noble (EPMC Awardee)Michael Waring (EPMC Awardee)Sam Butterworth (EPMC Awardee)

Related Research

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Original classification

Biomedical Resources Grant

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