Measurement validation of novel nuclear-targeting DNA as next generation therapies

作为下一代疗法的新型核靶向 DNA 的测量验证

• 批准号: 10039373
• 金额: $ 2.06万
• 依托单位: TOUCHLIGHT IP LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10039373
• 关键词: Measurement; validation; novel; nuclear; targeting

With the development of new DNA-based therapies and technologies the demand for nucleic acid products continues to increase. The requirement for large quantities of high-quality DNA and the need to produce more difficult sequences for advanced therapeutics have brought the production of DNA to its limits. Current methods of DNA manufacture rely on bacterial fermentation which suffers from both manufacturing capacity issues and low sequence stability during bacterial growth.Touchlight's synthetic biology DNA production process overcomes the current limitation of bacterial fermentation using enzymatic means of production. This _in vitro_ DNA technology is able to produce large-scale, high-quality constructs using a DNA polymerase to amplify DNA templates and a protelomerase to cleave and ligate amplified DNA into minimal cassettes for use in therapeutics and synthetic biology applications. Continuous developments in the process have resulted in both increased capacity and reduced footprint for DNA manufacture alleviating some of the current bottlenecks associated with nucleic acid productionAlthough large advances in this process have been made in DNA manufacturing a greater understanding of how DNA behaves in a cellular context will allow the production of improved DNA products and platform.Touchlight has developed new DNA constructs with improved cellular and nuclear targeting abilities resulting in increased protein expression however the limited knowledge and ability to monitor DNA within a cell makes further optimisation challenging. A more detailed understanding of the DNA subcellular localisation is therefore essential for the continuing improvement of Touchlight's core constructs.The knowledge generated from this project will increase Touchlight's ability to satisfy DNA demand and will contribute directly to improving human health. Translated improvements in nuclear entry efficiency for Touchlight's leading _in vitro_ DNA manufacturing process will help meet the increasing demand of DNA constructs from Industrial partners and decrease the costs of DNA therapeutics.

随着新的基于 DNA 的疗法和技术的发展，对核酸产品的需求不断增加。对大量高质量 DNA 的需求以及为先进疗法生产更困难的序列的需要已经使 DNA 的生产达到了极限。目前的DNA制造方法依赖于细菌发酵，这种方法在细菌生长过程中存在制造能力问题和序列稳定性低的问题。Touchlight的合成生物学DNA生产工艺克服了目前使用酶促生产方式的细菌发酵的局限性。这种体外 DNA 技术能够使用 DNA 聚合酶扩增 DNA 模板，使用原核端粒酶将扩增的 DNA 切割并连接到最小的盒中，从而产生大规模、高质量的构建体，用于治疗和合成生物学应用。该工艺的持续发展提高了 DNA 制造的产能并减少了占地面积，从而缓解了当前与核酸生产相关的一些瓶颈。尽管该工艺在 DNA 制造方面已取得了巨大进步，但对 DNA 在细胞环境中如何行为的更深入了解将允许生产改进的 DNA 产品和平台。Touchlight 开发了新的 DNA 构建体，其具有改进的细胞和核靶向能力，从而增加了蛋白质表达 监测细胞内 DNA 的知识和能力有限，这使得进一步的优化具有挑战性。因此，对 DNA 亚细胞定位的更详细了解对于 Touchlight 核心结构的持续改进至关重要。该项目产生的知识将提高 Touchlight 满足 DNA 需求的能力，并将直接为改善人类健康做出贡献。 Touchlight 领先的体外 DNA 制造工艺的核进入效率的转化改进将有助于满足工业合作伙伴对 DNA 构建体日益增长的需求，并降低 DNA 治疗的成本。