Development of a technology to certify engineered DNA molecules

开发验证工程 DNA 分子的技术

• 批准号: 10509988
• 负责人: Jean M Peccoud
• 金额: $ 38.8万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10509988
• 关键词: Address; Affect; Algorithms; Architecture; Bar Codes; Biological; Biological Process; Biological Sciences; Biological Testing; Biology; Biomedical Research; Biotechnology; Blood Circulation; Cell Therapy; Certification; Clinical Research; Code; Communities; Complex; Computer Security; Computers; DNA; DNA Sequence; Data; Database Management Systems; Development; Documentation; Elements; Engineering; Ensure; Event; Fostering; Funding; Gene Expression; Generations; Genetic; Genetic Engineering; Genome engineering; Individual; Industry; Infrastructure; Knowledge; Label; Link; Methodology; Methods; Modification; Molecular; Mutate; Mutation; Names; Persons; Pharmaceutical Preparations; Plasmids; Play; Production; Property; Publications; Recombinants; Recording of previous events; Records; Reproducibility; Research; Resources; Role; Safety; Scheme; Scientist; Secure; Security; Signal Transduction; Software Engineering; Standardization; System; Technology; Testing; Therapeutic; Tube; United States National Institutes of Health; Validation; Variant; Visualization software; Writing; base; bioinformatics pipeline; biological research; computer network; cryptography; design; digital; engineering design; expression vector; follow-up; gene therapy; genetic element; improved; innovation; medical specialties; new technology; online resource; research and development; response; technology validation; therapeutic protein; tool; vaccine development; web site

PROJECT SUMMARY The open availability of authenticated, well-documented research materials is essential for scientific progress. Plasmids have become essential research tools to address almost any question in biology, and together with other forms of engineered DNA molecules, are essential for clinical research applications including gene therapy, vaccine development, and the production of recombinant drugs. Currently, the two common links between a plasmid and its documentation are the plasmid names and the plasmid sequence. Despite the central role that plasmids play in biomedical research and development, there is no guaranteed way to connect a physical plasmid in a tube to its documentation. A pipetting error, a labelling error, a spontaneous mutation, or an undocumented modification of the plasmid are some of the events that could result in a tube containing a different plasmid than what is indicated on the label. In addition, there is no standardized, secure approach to documenting the sequence, function, and lineage of a plasmid. As a result, there are widespread discrepancies between the physical sequences of the plasmids in circulation in the life science community and their supposed reference sequence. This situation creates reproducibility issues, slows down R&D efforts and raises significant security and safety issues for biotechnology applications. We are proposing to develop a new digital certificate technology, enabled by a web-based resource called MyPlasmid.org, that will provide a robust, physical link between engineered DNA molecules, their electronic documentation, and their authors. This technology will produce unique DNA sequences generated by cryptographic algorithms that can be inserted into an engineered DNA molecule. MyPlasmid.org will allow users to document their genetic designs by aggregating the documentation of individual genetic elements as well as combinations of elements. In addition, it will link the computer records of the engineered DNA sequence directly to the molecule itself and provide a method to retrieve documentation without a priori knowledge of the plasmid's identity. Short unique DNA sequences called certificates will be inserted between the functional blocks of engineered sequences. Unlike DNA barcodes, certificates will be computed by cryptographic algorithms using the DNA sequence itself and the author's identity as input so that users of engineered DNA molecules can verify the origin and integrity of certified DNA molecules. The technology described in this proposal is expected to foster a transition similar what has been observed in the semi-conductor industry where different stakeholders invest in the development of circuits that can be easily combined in larger designs that can then be manufactured by foundries not involved in the chip design. By ensuring that the sequence, origin, function, and lineage of engineered DNA molecules is accurately tracked and conveyed to all users, the proposed technology will improve the reproducibility, utility, and potential application of engineered DNA molecules in the life sciences.

项目摘要 经过身份验证的，有据可查的研究材料的开放供应对于科学进步至关重要。 质粒已成为重要的研究工具，以解决生物学中的几乎任何问题，并与 其他形式的工程DNA分子对于包括基因疗法在内的临床研究应用至关重要， 疫苗开发和重组药物的产生。目前，两个共同的链接 质粒及其文献是质粒名称和质粒序列。尽管有核心角色 质粒在生物医学研发中发挥作用，没有保证的方法可以连接物理 质粒在其文档中的管中。移动误差，标签误差，自发突变或 质粒的无证件修改是一些可能导致包含不同的管子的事件 质粒比标签上指示的质粒。此外，没有标准化的安全方法 记录质粒的序列，功能和谱系。结果，存在广泛的差异 在生命科学界流通中质粒的物理序列与他们所假设的 参考序列。这种情况会引起可重复性问题，减慢研发工作并提出重大 生物技术应用的安全和安全问题。 我们建议开发一种新的数字证书技术，该技术由一个基于网络的资源来启用 myplasmid.org，将在工程DNA分子之间提供牢固的物理联系，它们的电子 文档及其作者。该技术将产生由 可以插入工程DNA分子的加密算法。 myplasmid.org将允许用户 通过汇总单个遗传元素以及 元素的组合。此外，它将直接链接工程DNA序列的计算机记录 到分子本身，并提供一种未经质粒的先验知识来检索文档的方法 身份。简短的唯一DNA序列称为证书，将在功能块之间插入 工程序列。与DNA条形码不同，证书将通过加密算法计算 DNA序列本身和作者作为输入的身份，以便工程DNA分子的用户可以验证 认证的DNA分子的起源和完整性。预计该提案中描述的技术将 促进过渡类似于半导体行业中观察到的情况，不同的利益相关者 投资可以在较大的设计中轻松合并的电路的开发，然后可以制造这些电路 由不参与芯片设计的铸造厂。通过确保序列，来源，功能和谱系 精确跟踪工程DNA分子并将其传达给所有用户，拟议的技术将 改善工程DNA分子在生命科学中的可重复性，效用和潜在应用。