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Scripps, Pfizer Collaborate on DNA-Coded Drug Discovery

DNA molecules

DNA molecule display (Christian Guthier, Flickr)

10 January 2017. Drug maker Pfizer Inc. is gaining access to advances in a synthetic chemistry technology developed by Scripps Research Institute that tags compounds with DNA identifiers. While Pfizer is paying Scripps a fee to access the technology, few other financial or intellectual property details were disclosed.

The agreement offers Pfizer an opportunity to adopt recent advances in DNA-encoded chemical libraries for drug discovery created at Scripps Research Institute labs in La Jolla, California. Current compound screening methods, known as high-throughput screening, adds test compounds individually to proteins to find binding actions to those proteins. And while these techniques employ robotics to speed and systematize the process that can screen millions of chemicals, that process is still laborious and expensive.

DNA-encoded libraries add unique pieces of DNA to small molecule, or low-molecular weight compounds used to test for activity against target proteins. Adding these DNA tags gives each compound a unique identifier, like a bar code, making it possible to screen many times more chemicals simultaneously against target proteins. Because of the unique DNA identifiers, candidate compounds can be more easily highlighted once binding occurs with the protein target. Scripps says DNA coding enables the screening of compounds numbering in the billions, rather than millions, sharply increasing the speed and efficiency of early drug discovery.

The concept of DNA coding for drug discovery was introduced in the 1990s by Scripps researchers Richard Lerner and Sydney Brenner, but practical applications of the technology required further advances in DNA sequencing and informatics. A review of the technology by Nature in February 2016 notes a number of biotechnology enterprises in the U.S. and Europe are developing DNA encoded libraries, with pharma company GlaxoSmithKline acquiring one of those companies, Praecis Pharmaceuticals for $55 million. Drug makers Novartis and Roche, says Nature, are building in-house capabilities.

In the agreement with Scripps, Pfizer is gaining access to the institute’s latest advances in DNA coded libraries. Pfizer scientists with work with several Scripps chemistry researchers and labs to adapt Scripps’s advances to Pfizer’s drug discovery processes. The current agreement, say the parties, is seen as a first stage in a project that could expand later on to include licensing related technologies.

In February 2016, Scripps chemistry researcher Brian Paegel and colleagues published a paper describing one of those advances, the synthesis of miniaturized DNA-encoded compound libraries. In this process, the DNA identifiers are contained in microscopic beads that attach chemically to the compounds, with one bead connected per compound. An associate of Paegel says in an institute statement that the “one bead-one compound” tagging scheme makes it possible to attach unique identifiers to millions of compounds in one week for about $500.

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Disclosure: The author owns shares in Pfizer.

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