Speeding drug discovery

Advanced animal model generation and production technologies can change the game for investigators, accelerating drug discovery and optimizing research success.

Dr. Holger Kissel

The pharmaceutical industry is facing unprecedented competitive pressures and economic challenges. In this climate, the ability to speed, streamline and improve the efficiency and productivity of drug discovery is more vital than ever.

Lab animal models continue to play a key role in the success of in vivo studies. To develop effective therapeutic mechanisms, researchers need relevant models uniquely suited to the disease under study. As important as the model's suitability is access to the model on a fast timeline, since speed of access directly affects the speed of drug discovery, the cost of drug development, and time-to-market with new, competitive products. With the right model on the right timeline, investigators can obtain insightful data faster, reduce research costs and minimize the risk and consequences of late-stage failures.

Through advances in the technologies used to design, generate and produce lab mice and rat models, investigators can leverage sophisticated tools to improve drug discovery and gain a competitive advantage.

Custom Models Made Easy

Genetic engineering advances have made it possible to develop models precisely suited to a specific in vivo study. Yet, custom design and development traditionally involved long lead times that slowed the process and hampered competitive position. New, sophisticated technologies like those employed by Taconic greatly reduce lead times, facilitating faster, easier access to off-the-shelf and custom generated models.

Various targeted gene mutation technologies facilitate faster development of custom models for target validation. These include constitutive or conditional gene knockout, conditional knockout with a Cre-ER gene switch, and targeted transgenesis, an efficient method for introducing transgenes into the genome. To improve compound testing and target validation, leading pharmaceutical companies also turn to advanced targeted gene replacement technologies, including constitutive knock-in of a gene, humanization (in which the murine gene is replaced with its human counterpart), and humanization with optional conditional knockout (deleting the humanized gene if needed). Perhaps the most cutting-edge technology to influence gene expression today is transgenic in vivo RNA inhibition. This technique involves inducing and reversing gene knockdown in adult mice, enabling greater insights into drug and target-related disease mechanisms.

Other model generation technologies allow researchers to eliminate custom development in some cases. Through off-the-shelf repositories of knockout mice and rats, suppliers like Taconic help accelerate drug discovery and speed time-to-market by eliminating custom development lead times. Knockout mice focus on knocking out novel protein targets in gene classes known to be amenable to pharmaceutical intervention. The availability of knockout rat models is a recent development, enabling the use of knockouts in studies in which rats are the preferred model, either due to their size or greater physiological similarity to humans.

Targeting a Single Kinase

As the key communicators throughout a cell's life, kinases play a critical role in nearly every known cellular process and an equally vital role in drug discovery. Targeting individual kinases is valuable for drug research, but designing drugs that only impact a single kinase has proven challenging. Now, technologies like those used at Taconic facilitate the development of models that inhibit a single kinase - empowering investigators to mimic exactly what occurs when a drug inhibits only that kinase in a clinical setting.

Appropriate for target validation and compound testing, the generation of analog-sensitive kinase alleles (ASKA) in Taconic's KinaseSwitch mice slightly modifies only the chosen kinase, making it sensitive to a well-characterized small molecule inhibitor without altering its function. This unique approach allows researchers to analyze a kinase's function in vivo, make more accurate predictions about a drug's efficacy, and determine if inhibition will cause undesirable side effects. By enabling the study of kinases so precisely and under physiologically relevant conditions, these models can greatly speed research and improve drug discovery.

Taking Transgenics to the Next Level

Transgenic animal models have always proven invaluable to drug discovery, since they enable altering specific genetic characteristics to produce a disease-specific model uniquely suited to a study's focus. That's why investigators employ transgenics in areas such as ADME-Tox, metabolic and cardiovascular disease, neurodegeneration, immunology, inflammatory disease, and endocrinology research. Programs like the Taconic Transgenic Model™ program, offering fully-licensed, off-the-shelf transgenics that eliminate the need to find, license and breed the right model, have long proven a staple for researchers. Now, technology is taking the use of transgenics to the next level.

Bioluminescent technology makes it possible to generate light-producing, disease-specific models that greatly aid in disease research and toxicology studies. Light-producing transgenics are especially suited to oncology, inflammation, endocrine and metabolic disease research, as well as imaging studies in these areas.

When Outsourcing Makes Sense 

Maximizing limited resources is a fact of life in drug discovery. Many organizations don't have the facilities, expertise, or staffing needed to breed lab animals in-house, yet they need assurance of reliability and prefer as much flexibility and control as possible. That's when contract breeding is a viable option.

Outsourcing animal breeding to a trusted partner enables investigators to obtain animals quickly and cost-effectively, free up space for research use, and focus staff on critical projects. Through completely customized programs and access to scientific experts in breeding, genetics and health, the investigator retains the flexibility to have a vendor manage his breeding programs in sync with research project needs. By outsourcing colony production, organizations can relieve in-house capacity constraints, reduce breeding costs (by avoiding capital investments), and keep staff focused on the core business of research. All this is generally done while simultaneously improving a  line's health status before breeding. For most breeding programs, a derivation of the line is conducted to assure health integrity. Our industry-leading IVF technology assures that this step can be completed quickly to keep your project on track. To protect the investment in a line, sperm or embryos can be cryopreserved - providing insurance against genetic drift, enabling startup of a line if needed, and preserving lines not currently in use for later access.

As drug discovery grows more complex, it's critical to rely on easy access to the most relevant animal models on the right timelines. Today's new technologies turn that goal into reality.