DNA Barcode Technology Enables Massive Simultaneous Drug Candidate Validation

A Korean research team has launched a public drug discovery service capable of screening and validating tens of millions of compounds simultaneously. Until now, such technologies were either available only to a limited number of companies with in-house platforms or had to be outsourced to expensive overseas service providers. The new public platform is expected to provide domestic industry, academia, and research institutes with more accessible and cost-effective hit discovery opportunities.

The Korea Research Institute of Chemical Technology (KRICT, President Seok-Min Shin) announced that its DNA-Encoded Library (DEL) Research Center has launched the "DEL CoreBank Platform," which supports hit discovery processes based on DNA-Encoded Library technology. The platform offers services ranging from compound library provision and screening to data analysis and follow-up validation.

DEL technology attaches unique DNA sequences to compounds like barcodes, allowing vast numbers of compounds to be distinguished and screened simultaneously. The technology is expected to complement conventional high-precision screening approaches by enabling ultra-large-scale hit discovery.

Drug discovery begins with the screening process, in which researchers identify hit compounds capable of binding to disease-related target proteins from among diverse chemical structures.

Conventional High Throughput Screening (HTS) methods analyze compounds individually in separate wells. Because binding reactions can be directly measured without additional molecular modifications, HTS provides high reliability.

However, if one million compounds must be screened, even using sixty 384-well plates per day would require about two months. As a result, screening extremely large compound collections involves substantial time and cost burdens, as well as large quantities of protein samples.

In contrast, DEL technology enables simultaneous screening by mixing compounds together in a single experiment. Even when the number of compounds exceeds tens of millions, the screening process can be completed within one month.

First, different chemical building blocks (BBs) and corresponding DNA barcodes are placed into 100 wells and chemically linked together. After mixing all compounds into a single solution, the mixture is redistributed into another set of 100 wells, where additional chemical structures and DNA barcodes are attached. This process generates 10,000 structurally distinct compounds. By repeating the synthesis-and-splitting cycle three times using 100 types each of building blocks A, B, and C, researchers can generate a mixed library containing one million compounds.

The compound mixture is then exposed to disease-related target proteins, followed by Next Generation Sequencing (NGS) to identify which DNA barcodes remain enriched after binding. This computational process decodes millions of DNA fragments and matches them to the original chemical structure database.

Because DEL experiments are performed in mixed solutions with DNA-conjugated compounds rather than pure compounds themselves, errors may occur, such as nonspecific binding to impurities or preferential amplification of certain DNA sequences. To address these issues, KRICT developed AI-based analysis methods trained on large-scale experimental datasets to identify structural patterns associated with stronger protein-binding affinity.

Among the surviving hit compounds, the top 50 compounds predicted to have the highest drug potential are selected through machine-learning-based data analysis, and a final report is provided. If requested, the platform also supports resynthesis of pure compounds without DNA barcodes and experimental validation against the user's target proteins.

The DEL Research Center has sought to overcome barriers such as the high cost of overseas DEL services and concerns over information leakage. Through 2027, while the project is supported by the Ministry of Science and ICT and the National Research Foundation of Korea under the "CoreBank Construction Project Based on a Large-Scale DNA-Encoded Library Platform," service fees will be temporarily reduced by 50%.

Daewoong Pharmaceutical, iLAB Inc., the National Cancer Center, Ewha Womans University, and GIST are among the organizations that have begun receiving support. Researchers can apply through the DEL Research Center menu on the Korea Chemical Bank website, and support will be provided after review of factors such as target overlap.

Dr. Jung-Nyoung Heo, Director of the DEL Research Center, stated, "We will help reduce Korea's dependence on overseas DEL technologies and support efficient domestic drug discovery processes from initial hit discovery to follow-up validation."

It is meaningful that advanced drug discovery services are now being provided to Korean researchers through a DEL CoreBank platform established with domestic technologies."

Seok-Min Shin, President, Korea Research Institute of Chemical Technology   

The DEL Research Center expects the platform to contribute to the discovery of small-molecule drug candidates for various diseases, including cancer, immune diseases, and infectious diseases, and to help translate early hit discovery into practical drug development outcomes.

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