Provenance attestation of human cells using physical unclonable functions

项目摘要 成簇的规则间隔短回文重复序列（CRISPR）技术的使用刺激了无数的 关键相关的应用程序 与本项目主题相关的是， 公司，大学和政府实验室，提供或需要定制的CRISPR为基础的 细胞系工程已经开始出现。可以预见，在不久的将来，对于每一个细胞系模型将存在 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 并且代表用户构成有价值的资产。 考虑到其中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 受益于能够保护与定制产品生产相关的知识产权的机制 工程细胞系，并能确保其质量。不幸的是，有效的细胞系来源证明 解决方案目前在该生态系统中不可用。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也导致许多细胞系问题，包括交叉- 污染、误认和从可疑或无证来源采购， 破坏了医学研究的鲁棒性、可重复性，最终破坏了医学研究的整体效率。 为了填补这一空白，在这里我们将重点放在一个最基本的安全原语，它可以支持完整性 和细胞系采购的问责制，即将独特的，强大的和不可克隆的 每个交易产品的标识符。SyntaxisBio及其研究合作伙伴德克萨斯大学 在达拉斯（UTD）旨在开发和验证一种技术，将使出处证明协议， 在细胞系分配网络中引入问责制。的 正在申请专利的技术， 物理不可克隆功能（PUF）最近在UTD（出现在科学进展）中开发， 用于在小区中引入唯一的、鲁棒的和不可克隆的标识符。 我们认为，遗传PUF可以实现一种来源证明协议，该协议不仅可以用于保护 细胞系生产商的知识产权，也可以增强客户对来源的信心。 并由此影响所获得的细胞系的质量。具体而言，基因PUF技术使生产商能够 一个有价值的细胞系，在每个合法生产的细胞中插入一个独特的，稳健的和不可克隆的签名， 细胞系的认证副本细胞系的生产者可以确保任何公开声称 该细胞系的复制品的所有权或使用权已合法获得。与此同时，细胞的用户 生产商可以确保其来源和质量，因为生产商明确确认其来源并假设 负责其生产。

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.