Accelerating analytics for gene therapy using enhanced mass photometry

基因治疗为许多使用传统药物难以预防或治疗的疾病带来了巨大的希望，包括遗传性疾病、罕见疾病和与年龄相关的疾病以及癌症。随着行业的发展，迫切需要更高效、更有效的质量控制测试技术。针对传统药物开发的技术在应用于复杂的基因疗法时存在很大的局限性，例如腺相关病毒（AAV）基因疗法，它使用病毒颗粒来传递可以帮助治疗或治愈疾病的基因。对于AAV疗法，一个重要因素是有多少载体颗粒携带靶基因，但目前测量这一点的方法既昂贵又耗时，通常需要外包。这造成了处理瓶颈，意味着测量通常只在生产结束时进行，即使这些信息在整个开发和生产过程中都是非常需要的。需要单独的分析来测量污染物，这进一步降低了效率。作为另一个重要的限制，没有可用的技术可以区分部分加载的颗粒和完整的颗粒。在这个项目中，我们建议使用质量光度法来解决这些挑战，我们开发的一种技术，使用最少的样品来测量单个颗粒的质量。我们相信这项技术可能会改变这一领域的游戏规则，因为初步实验表明，它可以超越目前的最先进技术。它可以测量负载颗粒的百分比，同时测量较小污染物的数量，它比目前的方法快15倍，便宜100倍。在这里，我们计划将质量光度法与现有方法进行基准测试，并进行改进，以更好地定制我们的方法以满足AAV载体表征的要求。（世界上唯一的质量测光技术生产商），谁将开发仪器，以及细胞和基因治疗弹射器，谁将提供AAV材料和进行基准测试，如果成功，该项目将提供一种变革性技术，帮助加速有前途的基因疗法的开发、生产、批准和安全使用。它将推动基因治疗行业的发展，为英国及其他地区带来经济和其他利益。针对一个快速增长的市场与上级，创新技术，该项目代表了一个健全的投资。也是及时的;目前正在制定这一领域的法规，为将这一技术纳入生产和质量控制过程创造了机会。

Gene therapy holds huge promise for many conditions that have been difficult to prevent or treat using conventional drugs, including inherited, rare and age-related diseases, and cancers. As the industry grows, there is an urgent need for more efficient, effective technologies for quality control tests. Technologies developed for traditional drugs have major limitations when applied to complex gene therapies, such as adeno-associated virus (AAV) gene therapies, which use virus particles to deliver genes that can help treat or cure disease.For AAV therapies, one important factor is how many vector particles are carrying the target gene, but current approaches for measuring this are expensive and time-consuming, and usually need to be outsourced. This creates a processing bottleneck and means the measurement is usually done only at the end of production, even though such information is highly desirable throughout development and production. Separate assays are needed to measure contaminants, creating further inefficiencies. As another important limitation, no available technology can distinguish partially loaded particles from full ones.In this project, we propose to address these challenges using mass photometry, a technology we developed that measures the mass of single particles using minimal sample. We believe this technology could be a game-changer in this area because preliminary experiments show it can outperform the current state-of-the art. It can measure the percentage of loaded particles while simultaneously measuring amounts of smaller contaminants, and it is up to 15-fold faster and 100-fold cheaper than current approaches. Here, we plan to benchmark mass photometry against existing approaches and also make improvements, to better tailor our approach to the requirements of AAV vector characterisation.The project is a collaboration between Refeyn Ltd (the world's sole producer of mass photometry technology), who will develop the instrument, and the Cell and Gene Therapy Catapult, who will provide AAV material and conduct benchmarking.If successful, this project will deliver a transformative technology, helping accelerate the development, production, approval and safe use of promising gene therapies. It will advance the gene therapy sector, bringing economic and other benefits for the UK and beyond. Targeting a rapidly growing market with a superior, innovative technology, this project represents a sound investment. It is also timely; regulations are now being formed in this area, creating an opportunity to embed this technology in production and quality control processes.