Dedicated to unleashing the transformative potential of DNA-encoded libraries (DELs) in drug discovery, I am committed to empowering scientists to utilize this technology effectively. Leveraging extensive technical expertise and consulting experience with DELs, I offer tailored guidance to clients across all aspects of this innovative approach. With comprehensive knowledge and unwavering objectivity, I am dedicated to facilitating your success in harnessing the power of DELs to drive life-changing innovations.
About DNA-Encoded Libraries
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The Revolutionary Power of DNA-Encoded Libraries
Imagine a scenario where you could assess the binding of billions of molecules to your target within hours and without specialized equipment. Such a capability would unlock unprecedented possibilities in the life sciences. This is precisely what makes DNA-encoded libraries (DELs) so revolutionary. DELs empower scientists to sample chemical libraries of unmatched size and diversity using a streamlined affinity selection protocol. It is no surprise that within just a few years, DELs have advanced from an obscure technology to a cornerstone in pharmaceutical hit discovery. Countless success stories from diverse teams underscore the profound impact of DELs in uncovering novel chemical entities. However, what we have witnessed thus far may only be the beginning of even more transformative breakthroughs. By integrating them with cutting-edge technologies such as machine learning and structure-based drug discovery, conducting selections in living systems, and expanding their reach to new target classes, DELs promises to reshape the life sciences landscape. Staying ahead in DEL innovation will be imperative for any bioscience unit aspiring to be at the forefront of pharmaceutical advancements.
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DNA-encoded libraries unleash revolutionary innovations
The power of DELs originates from ingeniously connecting chemical structures of library molecules to easily readable DNA sequences. By leveraging modern DNA amplification and sequencing technologies, linking molecules to DNA barcodes allows for the seamless conversion of chemical structure into data suitable for computer processing. DNA-encoding enables the identification of target binders through a simple affinity selection protocol. During selection, just a few microliters of a DEL are incubated with an immobilized target, followed by wash steps to remove low-affinity binders. The retained molecules are then easily identified through PCR amplification and DNA sequencing. Remarkably, this entire process takes only a few hours, without the need for target-specific bioassays and using readily available equipment. By sequencing the DNA barcodes, enriched molecules are indicated as potential target ligands. This streamlined workflow not only expedites drug discovery and cuts costs but also has the potential to democratize medicinal chemistry. By granting access to hit discovery methodology to scientists without advanced high-throughput screening infrastructure and enabling exploration of investigational drug targets, DELs pave the way for a more inclusive and innovative future in drug discovery.
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Overcoming Challenges to Achieve Reliable Results
Even users with a good understanding of DEL fundamentals often encounter challenges due to the opaque nature of DELs. Users typically have limited insights into the structures, building blocks, and synthetic protocols used to prepare DELs, which are crucial for reliable results. Problems during selection protocols and statistical effects can also impact the reliability of DEL data, making hit triaging challenging. Therefore, a solid understanding of DEL principles is essential to avoid delays and prioritize genuine hits. Our mission is to assist scientists in successfully navigating this technology. We offer guidance, critically evaluate DEL resources and processes, and provide expert reviews of research plans. Sometimes, an external perspective is all that's needed to prevent costly failures.
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Emerging Opportunities
Currently, DELs are primarily used for the discovery of small-molecule binders to protein targets. However, this is just the tip of the iceberg in terms of the potential applications of DELs. Exciting new areas of research are emerging, such as the integration of DELs with machine learning (ML) methodologies. ML has the potential to revolutionize drug development, but obtaining large and useful datasets is a challenge. DELs can address this by providing datasets that map out the interactions between small molecules and their targets. However, it is crucial to understand the intricacies and limitations of DEL data to effectively implement ML approaches. In addition to supervised ML, alignment-based methods and combinations with structure-based approaches show great promise for drug development. Furthermore, there is growing interest in novel screening protocols, including photo-affinity approaches, DELs for covalent inhibitor discovery, and selections under physiologically relevant conditions. DELs specific to discovering molecular degraders and RNA-targeting molecules are also of high importance. Our consulting services can provide an updated evaluation of the current state of the art and help identify future opportunities as they arise.
About DELgineering Consulting
My mission is to advance DNA-encoded libraries (DELs) and promote their widespread adoption by guiding researchers in their initial stages. As an early believer in this cutting-edge technology, I am confident that its potential has yet to be fully realized. In an industry often driven by commercial interests, I offer an unwavering commitment to objectivity and a profound understanding of the intricacies behind DELs.
Trained as an oligonucleotide chemist at Stanford University and working in the group of Dr. Dario Neri, a DEL pioneer, I have an extensive knowledge of the technical nuances involved. My independent research focuses on advancing our understanding of the fundamental principles, opportunities, and challenges of DELs, allowing me to offer practical advice and suggest best practices for their implementation.
Throughout my career, I have contributed to significant advances that have propelled the field forward. For instance, we have successfully explored target-focused libraries, providing an economical DEL option with high data quality. We have pioneered alignment-based methods that streamline lead prediction within DELs. Additionally, our work has shed light on the critical effects of linkers, critical for the integration of DEL data with machine learning.
To share my expertise with a broad audience, I have authored 13 publications, 3 review articles, and 4 book chapters. I am an active member of the DEL community engaging through webinars and seminars as well as participating in meeting organization to stay connected with the latest developments and the thought-leaders in the field. Having served as a scientific consultant to more than 10 companies, I am enthusiastic about the prospect of providing my knowledge and experience to assist you to innovate.
Services
DELgineering Consulting offers expert consulting services across all areas of DNA-encoded libraries and their use in drug discovery.
Examples of areas of consulting:
General understanding of DEL technology
Advantages and limitations of DELs
Methods of preparing and screening DELs
Designing DELs
Assessment of DEL quality
Use of DELs in drug discovery endeavors
Lead development of DEL hits
Understanding DEL selection data
Avoiding pitfalls
Comparing quotes and technologies
Past and Present Partners
Contact Us
We welcome your inquiries on how we can provide the most effective support for your needs.