Solution: Reducing animal numbers in transgenic breeding programmes

Genetically modified animals, particularly mice, are used widely in the biosciences. The number of genetically modified animals being used for research has more than doubled in the last 10 years, to the extent that nearly half of all animals in research are now those in transgenic mouse breeding programmes. In 2013, 2.03 million procedures involving genetically modified animals were conducted in the UK, with mice accounting for 90% of these.

The generation of genetically modified mice is a very costly and inefficient process that uses a considerable number of animals, many of which are used purely for breeding purposes and not for research. The process relies on female mice being made to think they are pregnant, termed pseudopregnancy, so the uterus is physiologically receptive to transplanted embryos. Pseudopregnancy is traditionally induced using vasectomised or sterile males and is a very inefficient process, requiring many more females to be mated than is necessary.

Ostara Bioscience has developed a novel pessary-based approach which has the potential to more effectively induce pseudopregnancy in recipient females. The vaginal pessaries contain substances that have been identified in mouse seminal fluid that mimic the beneficial effects of semen, replacing the need for vasectomised/sterile males and reducing by up to 50% the size of the pool of females used as potential embryo recipients.

Early, small scale proof of concept studies demonstrated improved pseudopregnancy rates using the pessary approach instead of sterile males. However to maximise uptake and confidence in the approach it is necessary to conduct larger studies in the laboratories of potential end-users. Using the CRACK IT Solutions technology partnering hub, Ostara worked with the NC3Rs to develop a ‘pitch’ for showcasing their approach to the wider scientific community and engage with new partners to help validate the technology further. Through the network of NC3Rs/CRACK IT contacts, Ostara has generated interest from 10 new potential collaborative partners including a large pharmaceutical company, large academic breeding institutes, smaller university breeding facilities, SMEs and an international society interested in the development and application of novel transgenic technologies.

Ostara has successfully applied for CRACK IT Solutions funding to work with the Cancer Research UK Transgenic Service to evaluate and further refine the original pessary in inducing pseudopregnancy.  They are also developing a programme of work with the UK transgenic breeding unit of a major pharmaceutical company to test the final formulation in a variety of scenarios.  The results of these new collaborative research programmes will hopefully demonstrate the applicability of the pessary approach for inducing pseudopregnancy and encourage wider uptake in the technology, substantially reducing the number of animals used in transgenic breeding programmes globally.