by The use of DNA encoded libraries (DELs) to screen for potential drug candidates originated in the late 1990s. Early adopters saw DNA encoding as a way to screen extremely large libraries of small molecules for biological activity in a highly parallel manner. By assigning each chemical compound a unique DNA tag, libraries with millions or even billions of molecules could be screened in a test tube rather than manually testing each compound one by one.
The first proof-of-concept DEL was created in 2001 by researchers at ComGenex, who chemically synthesized a library of 50,000 peptides each tagged with a unique Global DNA Encoded Libraries sequence. This initial library demonstrated that DNA could reliably link chemical structure to sequence for high-throughput screening. Over the next decade, new DNA synthesis and sequencing technologies enabled the creation of increasingly larger and more complex DELs at companies such as Hybrigenics, Anthropic, and Enumeral Biomedical.
Today’s DEL platforms can encode libraries with trillions of diverse structures thanks to rapid DNA synthesis and next-generation sequencing. Complex chemical variations such as non-natural amino acids, diverse linkers, and warheads can be encoded to maximize screening potential. State-of-the-art DEL screening assays use high-throughput sequencing to identify DNA sequences selectively enriched through interaction with a biological target of interest.
Benefits Of DNA-Encoded Screening For Drug Discovery
DNA-encoded screening provides several key advantages over traditional high-throughput screening techniques:
– Scale: DNA encoded libraries allow screening of chemically diverse libraries far beyond the capacities of plate-based screening, which is limited to roughly one million compounds. Trillion-member DELs expand the chemical space that can be explored.
– Precision: DNA sequencing precisely determines which molecules in the library interact with the target. This enables hits to be rapidly identified down to parts-per-billion sensitivity.
– Efficiency: By testing millions of structures simultaneously in a single tube reaction, DNA-encoded screening is significantly more efficient than individual compound assays. Hit rates are also generally higher due to the vast areas of chemistry explored.
– Molecular Diversity: DNA encoded libraries incorporate chemistries like linkers, non-natural amino acids, and warheads that expand beyond “drug-like” spaces of traditional compound collections. This uncovers novel mechanisms of action.
– Automation: Once established, DEL screening platforms are highly automated and consume only small amounts of target. This allows rapid evaluation of hundreds of biological targets.
Global Impact And Future Directions
Since the first DEL proof-of-concept in 2001, DNA-encoded screening has advanced significantly thanks to collaborations between academia and private worldwide. Global DEL players are now developing innovative new library compositions along with improved screening assays and data analysis:
– San Francisco- Based Anthropic is leveraging AI to design highly tailored DNA encoded libraries for specific protein family drug targets. Their goal is AI-guided discovery of novel therapeutic mechanisms.
– Cambridge- UK based Abcam has launched the Abcam DNA-encoded chemical library to enable DEL screening through their global distribution network and extensive portfolio of recombinant proteins and cells.
– Beijing- based BGI has established DNA encoded libraries capabilities as part of the China National GeneBank and screens novel targets to uncover first-in-class drugs, particularly for diseases prevalent in Asia.
– Australian company Lumos Diagnostics is developing tailored DELs, along with point-of-care sequencing, for rapid identification of effective antimicrobial compounds to combat antibiotic resistance globally.
As DNA synthesis and sequencing continue increasing in speed and decreasing in cost, DEL technologies will become applicable for an even wider range of drug discovery programs worldwide. Areas of future innovation include in vivo-encoded libraries for examining compound properties within living systems, as well as clinical DELs encoded directly within patients’ genomes to enable personalized medicine approaches. With continued worldwide collaboration, DNA encoded libraries holds immense promise to revolutionize global drug development in the decades to come.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
About Author - Ravina Pandya
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. With an MBA in E-commerce, she has an expertise in SEO-optimized content that resonates with industry professionals. LinkedIn Profile
