Every year, thousands of mice at the Cancer Research UK Cambridge Institute receive painful injections of tamoxifen, a drug that triggers genetic switches in cancer studies. This matters because tamoxifen is essential for turning genes on or off in mice to study cancer, but current delivery methods cause significant harm. Standard approaches—repeated injections into the abdomen or forced feeding via a tube—cause pain, stress, and marked weight loss, risking animal death. The drug also tastes bitter, so mice avoid it in food, making oral dosing unreliable. These problems produce inconsistent experimental results and require more animals to compensate. Fluid Pharma has developed tamoxifen-coated micro-pellets that mice eat voluntarily without aversion. The CRUK Cambridge Institute will test whether these pellets deliver consistent drug levels in the blood, achieve the same gene-switching effect as injections, and eliminate weight loss. If validated, this product could replace over four thousand injections given at the institute in the last three years alone. Success would mean fewer painful procedures, less animal stress, and more reliable data from fewer mice. Wider adoption across UK and international labs could transform how fundamental cancer genetics research is conducted.
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Tamoxifen (TAM) is widely used as a powerful approach to achieve conditional gene knockout (alteration) in mice by inducing temporal and spatial gene expression or deletion using Cre/loxP models. Standard administration protocols for TAM involve repeat dosing by Intra-Peritoneal (IP) injection or Oral Gavage (OG) over several days, both of which are invasive and have the potential to cause pain and stress in experimental animals. The oral feed route is also challenging due to poor palatability of TAM, causing food aversion. Mice dosed with TAM using traditional methods experience marked weight loss during the dosing period, leading to risk of morbidity in animals. Additionally, TAM’s limited solubility in dose vehicles complicates dose preparation, resulting in inconsistency and poor reproducibility of experimental results. Fluid Pharma, a UK biotech, have developed a highly palatable and easy-to-administer oral feed formulation of TAM, comprising drug coated micro-pellets. Preliminary data from this new product have demonstrated that there is no apparent weight loss in animals administered at effective dose of TAM via the feed route and that similar gene recombination efficiency can be obtained when compared to an equivalent OG dosing regimen. Fluid Pharma aims to establish partnership with a new user, CRUK Cambridge Institute (CRUK CI) to implement the product in their laboratories and to further validate that it is fit-for-purpose for wider adoption. CRUK CI use TAM induced gene expression routinely in the study of cancer and are very familiar with the challenges of TAM administration. The Institute operates with an infrastructure of independent core facilities, bringing together technical specialists from different scientific disciplines to support the academic research groups. This has resulted in a proven track record to deliver grant-funded innovation projects, making the CRUK CI ideal for this partnership. In this proposal, CRUK CI will conduct a series of stepwise experiments to achieve the following scientific objectives, for research groups to have the confidence to adopt this new technology: Standardisation of feed administration protocols for practical bead use in a preclinical animal unit Product characterisation through investigation of the TAM pharmacokinetics (blood concentrations) when delivered in feed, providing evidence that the beads are delivering adequate and reproducible TAM exposure to mice Validation of gene regulation using the palatable TAM beads via oral feed The project is driven by an urgent 3Rs need in preclinical research and aims to achieve immediate and wider, long term 3Rs impact. In the last 3 years, there have been over four thousand IP injections of TAM to mice at the CRUK CI. A successful validation of this new technology would have the immediate Refinement impact of reducing the number of IP injections and associated stress to the animals. In the longer term, fewer animal interventions and adverse effects associated with TAM administration have the potential to result in higher quality data outputs and a Reduction in animal numbers used. The wider impact would be the adoption of this technology both nationally and internationally in preclinical research. A new product proven to deliver a similar TAM induction effect to the more traditional routes of administration has the potential to result in very significant 3Rs benefits.
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