Znomics Drug Discovery Platform

Despite the sequencing of the human genome and heavy investment in new technologies such as gene chips and combinatorial chemistry, over the past 25 years the pharmaceutical industry has suffered from an inadequate pipeline of new drugs. Pharmaceutical companies need better ways to analyze the complex biology of animals and disease so as to increase the productivity of drug discovery.

The Znomics Drug Discovery Platform improves speed and efficacy while reducing costs related to the discovery of new drugs and drug targets.

Shifting the Paradigm

The Challenge: The current paradigm for drug discovery relies on developing and testing a compound on the basis of its activity against one target at a time (generally a receptor, ion channel or enzyme), in a cell-based assay. There are two problems with this approach. First, identifying the correct target(s) for drug screening in a given disease indication has proved to be extremely difficult. In clinical studies, many of the targets taken into drug screening have proven to be ineffective for the diseases in question. Second, while many effective pharmaceuticals act on a single target, other pharmaceuticals, such as Prozac (fluoxetine) and Effexor (venlafaxine), actually derive their efficacy through their action on multiple targets. Moreover, many important drugs, such as the diabetes drug metformin, exert their effects through unknown mechanisms. An ideal solution to these challenges in drug discovery would be to screen drugs for their activity against disease processes in the whole (live) animal. But using the traditional standard -- disease models in rodents -- the time and cost involved make it impossible to effectively screen today’s large compound libraries.

The Solution: Combined with Znomics’ proprietary RIM technology, the Znomics zebrafish disease models offer a platform for drug development that is unmatched by any other currently used animal model, providing the potential for a true paradigm shift in the industry.

More Efficient: Because of its rapid reproduction and development capabilities, the zebrafish has proven to be a significantly more economical model than other animals in which gene modification is possible, such as rodents.

More Effective: Enabling high-throughput, in vivo (live animal) drug screening in a vertebrate, zebrafish disease models not only address the problems inherent in the traditional single-target approach, in vivo screening also makes efficacy and toxicity data immediately available.

Enhancing the Current Standard

The Challenge: Pharmaceutical and biotechnology companies are generating large numbers of putative drug targets using genomics approaches such as microarray analysis. Current methods for validating and prioritizing these putative targets include deleting the gene (gene knock-out) from the mouse genome or developing chemical antagonists. These methods are extremely time-consuming and cost intensive.

The Solution: Combined with Znomics’ proprietary RIM technology, the Znomics zebrafish disease models offer the potential for improving the efficiency of the prevailing single-target approach to drug target discovery.

Powered by Advanced Database Technology: The Znomics Libraries comprise a comprehensive database capable of containing catalogued mutations in most zebrafish genes. As each insertion is identified, entered and annotated in the database, sperm harboring these insertions are cryogenically preserved to maintain the mutated lines. These archived sperm samples are used for in vitro fertilization to generate live zebrafish lines carrying defined mutations. Znomics partners with researchers around the world to use these zebrafish mutants as powerful and cost effective tools to study gene functions and discover drug targets.

Driven by Automated Assays: High-throughput, in vivo screening allows compounds to be screened simultaneously against all accessible drug targets for a given indication in a live vertebrate, greatly increasing the odds of finding effective drugs. Data on drug efficacy and toxicity becomes immediately available through these in vivo screens. Automated assays of physiological function being developed by our scientists will be used to provide more rapid phenotypic characterization of knockout animals and drug target validation.

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