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: 10834772
• 负责人: ALEXANDER PERTSEMLIDIS
• 金额: $ 1.38万
• 依托单位: SYNTAXISBIO, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10834772
• 关键词: Accountability; CRISPR/Cas technology; Cell Line; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Custom; Ecosystem; Engineering; Ensure; Future; Genetic; Health; Human; In Vitro; Intellectual Property; Investments; Laboratories; Legal patent; Medical; Medical Research; Modeling; Ownership; Phase; Production; Protocols documentation; Publishing; Reproducibility; Research; Science; Security; Small Business Technology Transfer Research; Source; Technology; Texas; Time; Transact; Universities; experimental study; genome editing; pre-clinical; research and development; success; trustworthiness

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 at UTD (published 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.

项目摘要 使用定期间隔短的短质体重复序列（CRISPR）技术的使用刺激了 无数申请非常相关 与人类健康，与该项目的主题相关的生态系统 公司，大学和政府实验室提供或需要定制的CRISPR- 基于细胞系的工程已经开始浮出水面。对于不久的将来，对于每个细胞系模型 将存在数百个自定义版本，每个版本都需要代表研发投资 生产商并代表用户构成有价值的资产。 考虑到使用此类细胞系的医学和生物医学应用的重要性 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 受益于可以保护与自定义生产相关的知识产权的机制 设计的细胞系，可以确保其质量。不幸的是，有效的小区出处证明 本生态系统中目前尚不可用的解决方案。除了限制细胞系生产者的能力 利用他们的投资，缺乏这样的解决方案还导致许多细胞系问题 可疑或无证来源的污染，错误识别和采购，这反过来又 破坏了鲁棒性，可重复性以及最终的医学研究总体效率。 为了填补这一空白，在此，我们专注于可以支持诚信的最基本安全基础之一 和细胞系采购的问责制，即与独特，坚固且无统治的能力 每个交易产品的标识符。此处，语法及其研究合作伙伴德克萨斯大学 在达拉斯（UTD）的目标 在单元线分布网络中介绍问责制。这 申请专利的技术称为遗传物理 最近在UTD开发了无统治的功能（PUF）（在科学进步中出版），并习惯于 在细胞中引入独特，健壮且无统一的标识符。 我们认为遗传PUF可以实现出处证明协议，不仅可以用于 保护细胞系生产商的知识产权，同时也要加强客户对 来源，因此，采购的单元线的质量。具体而言，遗传PUF技术使 在每个合法生产的每个合法生产中插入独特，坚固且无统治的签名的有价值的细胞系的生产商 并认证的单元线副本。细胞系的生产者可以确保任何公开声称的人 该单元线的所有权或使用副本已合法地获取了它。同时，单元的用户 可以确保生产商明确确认其起源并假设生产者的来源和质量 对其生产的责任。