Transposagen Biopharmaceuticals Inc. is a privately held biotechnology company that is dedicated to providing unique animal models of human diseases for drug discovery and development. Transposagen is currently focusing on the $1.2 billion/year rodent model market. The rodent model market is experiencing double digit annual growth due to the research and development needs of the pharmaceutical industry.
Rodent models are a necessary component for drug discovery research. The top 100 best-selling drugs in the United States, accounting for over $110 billion in annual sales, address only 43 targets. The majority of these targets (85% of the 43 targets) have been amenable to drug development through the availability of a corresponding rodent gene knock-out model. Recent analyses suggest that there are hundreds or even thousands of additional drug targets available in the human genome. Discovering new drug targets, and developing new therapeutically-relevant small molecules that interact with these targets, requires biological validation in animal models.
About 89% of all compounds tested for drug use fail during the final stages of approval due to unacceptable side effects or a lack of efficacy, typically after investments of more than US$400 million. There is a clear need to screen drugs in animal models that better reflect human physiology and toxicology before entering the most expensive phases of drug testing in humans.
While mice have proven to be a useful rodent model and techniques have been developed for routine disruption of their genes, in many circumstances rats are a superior laboratory animal for studying and modeling human disease. In many ways, rats are physiologically more similar to humans than are mice. For example, rats have a heart rate similar to that of humans, while mice have a heart rate five to ten times as fast. The rat is a better model than the mouse for human cardiovascular disease, diabetes, arthritis, and many autoimmune, neurological and behavioral disorders. In addition, rat models are superior to mouse models for testing the pharmacodynamics and toxicity of potential therapeutic compounds, partially because the number and type of many of their detoxifying enzymes are very similar to those in humans. Their larger size make rats more conducive to study by instrumentation, and also facilitates manipulation such as blood sampling, nerve conduction, and performing surgeries. Unfortunately, a number of technological obstacles have made it very difficult to produce rat knockout models of human diseases.
Transposagen has solved these technological obstacles by developing a platform technology that permits random mutagenesis directly in the germ cells (sperm and oocytes) of mammalian model organisms, including rats. Transposagen has the only technology that can efficiently create novel mutations in the rat, and rapidly determine the location of the mutation. The company is designing a new method using mobile DNA elements (or “jumping genes”) for the rapid and economical production of a large variety of mouse and rat models of human disease, which will enable a greater scrutiny of candidate drugs and will facilitate more favorable testing in humans. This unique technology has been used to produce gene knockout models in mice and rats, and is called the MutaMouse Drug Target Discovery System and MutaRat™ Drug Target Discovery System, respectively. Importantly, unlike other methodologies, this technology can be used to create models of human disease in other higher vertebrates such as rabbits, or primates, thus giving Transposagen a competitive advantage in the production of these model organisms.