COPENHAGEN, DENMARK — February 17, 2021 — Vipergen ApS announced today a published study describing a powerful new drug discovery approach that enables, for the first time, screening DNA-encoded small-molecule libraries (DELs) inside living cells. The study, published in the peer-reviewed Journal of the American Chemical Society, highlights the potential of Vipergen’s Cellular Binder Trap Enrichment® (cBTE) technology to significantly expand the ability to discover novel small molecules, including against difficult-to-drug targets, and reduce attrition rates in drug discovery. Vipergen is offering its cBTE DNA-encoded library drug discovery platform as a service to biotechnology and pharmaceutical company partners to accelerate and improve their drug discovery processes.
“This research validates the potential for Vipergen’s Cellular Binder Trap Enrichment platform to become a revolutionary tool in small-molecule drug discovery based on its ability to successfully screen DELs against drug targets inside living cells, with no requirement for purified active target protein,” said Nils Hansen, PhD, chief executive officer of Vipergen. “We expect the ability to perform DEL screening under the more physiologically relevant conditions of a living cell to significantly lower attrition rates in drug discovery. Furthermore, by uniquely allowing us to eliminate the requirement for highly purified active target protein, this technology will improve timelines and bring about new options for novel drug development by allowing us to screen many more targets, prioritize those giving the most promising screening results, and screen DELs against challenging targets that are difficult to express and purify in an active form. We look forward to providing this new tool to biotechnology and pharmaceutical partners to substantially improve the efficiency and success of their small-molecule drug discovery efforts.”
Screening technology plays a major role in small-molecule drug discovery, where the goal is to identify compounds that interact in a desired way with a drug target of interest to serve as starting points for drug development. Depending on the technology, conventional high-throughput screening technologies allow for testing of up to a few million molecules organized as libraries of discrete compounds. Screening campaigns are typically costly and time-consuming endeavors, from the initial conception of an assay through its translation into a format compatible with high throughput, large-scale experimentation and evaluation of results. DNA-encoded library (DEL) technologies—involving the attachment of unique DNA tags to each small molecule in a library that encodes its identity and how it was synthesized—have emerged as a game-changing tool to help overcome the significant time and cost constraints of conventional screening in drug discovery by enabling synthesizing and screening of libraries containing hundreds of millions to billions of small molecules simultaneously against a drug target of interest.
The results reported in the Journal of the American Chemical Society define Vipergen’s novel system for screening DELs inside a living cell under physiologically relevant conditions and without the need for highly purified active target protein. In this research, Vipergen scientists screened a 194 million-member DEL inside live oocytes of the South African clawed frog (Xenopus laevis) against three pharmaceutically relevant protein targets. The large size of the Xenopus oocyte permitted simple injection of the DEL, overcoming the fundamental challenge of delivering DELs across cell membranes for in vivo screening. The target protein was expressed in the oocytes fused to a prey protein to allow specific DNA labeling and to discriminate between DEL members binding to the target protein and the endogenous cell proteins. The technology successfully identified and validated multiple small-molecule hits for all three drug targets.
About Vipergen’s Cellular Binder Trap Enrichment®(cBTE) Technology
Vipergen’s proprietary Cellular Binder Trap Enrichment®(cBTE) is the first and only technology for screening DNA-encoded small-molecule libraries (DELs) inside a living cell. The platform is designed to accelerate and improve the success rate for discovering novel, high-quality small molecules for drug development—including against challenging drug targets that are difficult to express and purify in an active form—by:
- Lowering drug discovery attrition rates by enabling DEL screening under the more physiologically relevant conditions of a living cell
- Improving drug development timelines and expanding the DEL-amenable target space by eliminating the requirement for highly purified active target protein