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Applying synthetic biology to remove p24 impurities from the lentiviral product streams used in T cell engineering

应用合成生物学从 T 细胞工程中使用的慢病毒产品流中去除 p24 杂质

基本信息

批准号：
2415768
负责人：
金额：
--
依托单位：
University College London
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2415768
关键词：
Applying synthetic biology remove p24

项目摘要

Biopharmaceutical companies must contend with the bioprocess challenges posed by the presence of free, soluble p24 protein, also known as capsid or CA, in the lentiviral process streams used for cell and gene therapy products and their development. Free p24 has a propensity to form aggregates, can compromise the efficiency of gene transfer to target cells and may also confound p24-based estimates of virus production. Engineered, self-inactivating lentivirus is a key tool for both direct, virus-mediated gene therapy and for the ex vivo transduction of mammalian cells resistant to other methods of genetic modification, such as stem cells. With the emergence of T cells as a major new therapeutic product class, the importance of lentiviral engineering has only increased This project will establish if flexible linkers can be used to significantly alter the molecular weight and membrane-association properties of p24 so it no longer manifests to the same extent as a free, soluble protein in lentiviral product streams. Flexible linkers have a lengthy track record of application in fundamental research and biotechnology. Critically the project aims to achieve this p24 removal whilst preserving the performance of engineered lentivirus as a tool for efficient gene transfer to therapeutic T cells.

生物制药公司必须应对用于细胞和基因治疗产品及其开发的慢病毒工艺流中存在的游离可溶性p24蛋白（也称为衣壳或CA）所带来的生物工艺挑战。游离p24具有形成聚集体的倾向，可损害基因转移至靶细胞的效率，并且还可能混淆基于p24的病毒产生的估计。工程化的自失活慢病毒是直接的病毒介导的基因治疗和对其他遗传修饰方法（如干细胞）具有抗性的哺乳动物细胞的离体转导的关键工具。随着T细胞作为主要的新治疗产品类别的出现，慢病毒工程的重要性只会增加。该项目将确定是否可以使用柔性接头来显著改变p24的分子量和膜结合特性，使其不再表现出与慢病毒产品流中游离可溶性蛋白相同的程度。柔性接头在基础研究和生物技术中有着长期的应用记录。关键的是，该项目旨在实现这种p24去除，同时保留工程慢病毒作为有效基因转移到治疗性T细胞的工具的性能。