The development of immune-shielded genetic reporters for bioluminescence imaging

由于其在小鼠和人类中的免疫原性，Fluc系统目前在生物医学研究中没有发挥其真正的潜力。大多数BLI研究缺乏生物学相关性，因此降低了统计能力，而FLORC系统的报告工程可能会显著提高统计能力。我们和其他人对Fluc系统进行了大量的工程设计，以改善体内成像性能。我们的红外荧光素系统是独一无二的，通过提供更准确的近红外细胞成像，帮助克服生物医学研究中BLI有效性的问题。然而，到目前为止，还没有尝试设计出更好地保护小鼠免疫系统的FLOU。由于这一目标将导致动物使用的减少，它将很好地符合NC3R中的“成像生物工程组织”主题，并与卡迪夫大学的目标保持一致。这项工作将在两个方面对NC3R产生影响：a.通过改善BLI技术在干细胞研究中的吸收和扩大使用，以及b.通过提高干细胞研究的生物学相关性和信息量，从而改善干细胞治疗的临床前试验和临床应用之间的联系。改进翻译将对人类的预防、诊断和治疗战略产生影响，并导致在广泛的研究中改进和减少使用小动物和大动物，从单个实验的规模到更大规模的科学规划和生物医学和生物科学的长期方向。

Due to its immunogenicity in mice and humans the Fluc system does not currently fulfil its true potential in biomedical research. Most BLI studies lack biological relevance and therefore have reduced statistical power, which could be dramatically increased by reporter engineering of the Fluc system. We - and others have heavily engineered the Fluc system for improved in vivo imaging properties. Our infra-luciferin system is unique and helps overcome problems with the validity of BLI in biomedical research by providing more accurate near-infrared cell imaging. However, to date, there has been no attempt to engineer Flucs that better shielded from murine immune system. Since this aim would lead to a reduction in animal use it would fit well with the 'imaging bioengineered tissues' theme within the NC3Rs and in-line with the aims of Cardiff University. This work would impact on NC3Rs in 2 ways: a. by improving the uptake of, and extending the use of BLI technologies in stem cell research, and b. by improving the biological relevance and informativeness of stem cell research, hence improving the link between preclinical testing and clinical application of stem cell therapy. Improved translation will lead impact on prevention, diagnosis and treatment strategies in humans and lead to refinement and reduction in the use of small and large animals in wide-ranging research, from the scale of individual experiments to larger scale scientific planning and longer term directions in biomedical and biological sciences.