Provenance attestation of human cells using physical unclonable functions

使用物理不可克隆功能证明人类细胞的来源

• 批准号: 10603174
• 负责人: ALEXANDER PERTSEMLIDIS
• 金额: $ 36.16万
• 依托单位: SYNTAXISBIO, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603174
• 关键词: Accountability; Advanced Development; Authorization documentation; Bar Codes; Biological Models; CRISPR/Cas technology; Cell Culture Techniques; Cell Line; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Custom; DNA; DNA delivery; Data; Development; Disease model; Ecosystem; Electroporation; Engineering; Ensure; Foundations; Freezing; Funding Agency; Future; Genetic; Genetic Services; Genome; Genomics; Government; Government Agencies; Growth; Health; Human; In Vitro; Institution; Intellectual Property; Investments; Journals; Karyotype determination procedure; Laboratories; Lead; Legal patent; Libraries; Lipids; Location; Measurement; Measures; Medical; Medical Research; Methodology; Modeling; Monoclonal Antibodies; Output; Ownership; Phase; Play; Population; Pre-Clinical Model; Process; Production; Property; Protocols documentation; Publishing; Quality Control; Reading; Reporting; Reproducibility; Reproducibility of Results; Research; Role; Science; Security; Services; Short Tandem Repeat; Small Business Technology Transfer Research; Source; Technology; Texas; Therapeutic; Time; Transact; Universities; Vaccine Research; Validation; Variant; Viral; base; base editor; experimental study; falls; follow-up; genetic technology; genome editing; insight; interest; machine learning algorithm; novel; nuclease; operation; personalized medicine; pre-clinical; repaired; research and development; success; technology validation; trustworthiness; virtual

Project Summary The use of clustered regularly interspaced short palindromic repeats (CRISPR) technologies has spurred myriads of applications critically relevant to human health and, pertinent to the topic of this project, an ecosystem of companies, universities, and governmental laboratories that either offer or are in need of custom CRISPR-based cell line engineering has started to emerge. Foreseeably, in the near future, for each cell line model there will exist hundreds of customized versions, each requiring research and development investment on behalf of the producer and constituting a valuable asset on behalf of the user. Considering the significance of the medical and biomedical applications wherein such cell lines are used, as well as the importance of ensuring accuracy and reproducibility of the corresponding results, this ecosystem could benefit from mechanisms which can protect the intellectual property associated with the production of custom engineered cell lines and can ensure their quality. Unfortunately, effective cell line provenance attestation solutions are not currently available in this ecosystem. Besides limiting the ability of cell line producers to capitalize on their investment, lack of such solutions also results in numerous cell line issues including cross- contamination, misidentification, and procurement from dubious or undocumented sources, which in turn undermine robustness, repeatability and, ultimately, overall efficiency of medical research. To fill this void, herein we focus on one of the most fundamental security primitives which can support integrity and accountability of cell line procurement, namely the ability to associate a unique, robust and unclonable identifier with each transacted product. Herein, SyntaxisBio and its research partner The University of Texas at Dallas (UTD) aim to develop and validate a technology that will enable provenance attestation protocols to introduce accountability in cell line distribution networks. The patent-pending technology termed genetic Physical Unclonable Functions (PUFs) was recently developed in UTD (to appear in Science Advances) and is used to introduce a unique, robust and unclonable identifier in cells. We posit that genetic PUFs can enable a provenance attestation protocol which can be used not only for protecting the intellectual property of a cell line producer but also for bolstering the confidence of a customer in the source and, thereby, the quality of a procured cell line. Specifically, the genetic PUF technology enables the producer of a valuable cell line to insert a unique, robust and unclonable signature in each legitimately produced and authenticated copy of a cell line. The producer of the cell line can ensure that anyone who publicly claims ownership or usage of a copy of this cell line has acquired it legitimately. At the same time, the user of the cell line can be assured of its source and quality, as the producer explicitly confirms its origin and assumes responsibility for its production.

项目概要 成簇规则间隔短回文重复 (CRISPR) 技术的使用激发了无数人的兴趣 关键相关的应用程序 对人类健康以及与本项目主题相关的生态系统 提供或需要定制基于 CRISPR 的公司、大学和政府实验室 细胞系工程已经开始出现。可以预见，在不久的将来，对于每个细胞系模型都将存在 数百个定制版本，每个版本都需要代表生产商进行研发投资 并构成用户的宝贵资产。 考虑到使用此类细胞系的医学和生物医学应用的重要性，以及 由于确保相应结果的准确性和可重复性的重要性，该生态系统可以 受益于可以保护与定制生产相关的知识产权的机制 设计细胞系并可以确保其质量。不幸的是，有效的细胞系来源证明 该生态系统目前尚无解决方案。除了限制细胞系生产者的能力 充分利用他们的投资，缺乏此类解决方案也会导致许多细胞系问题，包括交叉 污染、错误识别以及从可疑或无证来源采购，进而 破坏稳健性、可重复性，并最终破坏医学研究的整体效率。 为了填补这一空白，我们在此重点关注可以支持完整性的最基本的安全原语之一 细胞系采购的责任，即关联独特的、强大的和不可克隆的细胞系的能力 每个交易产品的标识符。在此，SyntaxisBio 及其研究合作伙伴德克萨斯大学 达拉斯 (UTD) 的目标是开发和验证一种技术，使来源证明协议能够 在细胞系分配网络中引入问责制。这 正在申请专利的遗传技术 物理不可克隆函数 (PUF) 最近在 UTD 中开发（出现在 Science Advances 中），并且 用于在细胞中引入独特、稳健且不可克隆的标识符。 我们认为遗传 PUF 可以实现来源证明协议，该协议不仅可以用于保护 细胞系生产商的知识产权，同时也增强了客户对来源的信心 从而影响所采购细胞系的质量。具体来说，基因 PUF 技术使生产商能够 一种有价值的细胞系，可以在每个合法生产和使用的细胞中插入独特、强大且不可克隆的签名 细胞系的经过验证的副本。细胞系的生产者可以确保任何公开声明的人 该细胞系副本的所有权或使用权已合法获得。同时，该小区的用户 产品线的来源和质量可以得到保证，因为生产商明确确认了其来源并假设 对其生产负责。