Novel approach for T-cell genetic editing

生物技术的最新进展允许对动物和人类细胞进行遗传修饰，以用于研究和医学。这一领域非常有前途，很可能会改变未来的研究方式和治疗方法，特别是通过使用细胞作为药物。对于T细胞（一种能够对抗顽固性感染和某些癌症的免疫细胞）来说，这一点可能尤其正确。该项目将一种新的基因工程细胞方法（由生物技术公司Feldan开发）与蒙特利尔大学开发的T细胞处理专业技术相结合。具体来说，本申请的主要目的是开发和验证使用Feldan产品（航天飞机）进行遗传工程改造T细胞的最佳方法。穿梭机允许在细胞核内运送货物，遗传物质位于细胞核内。这种转运对细胞是无创伤的，因此与该领域的竞争方法相比可能具有明显的优势。因此，我们将使用穿梭机携带能够精确修改细胞遗传密码的蛋白质（通常称为CRISPR/Cas9系统）。虽然穿梭机可以用于遗传工程的几种细胞类型，费尔丹没有经验使用它在T细胞。蒙特利尔大学的Delisle实验室将提供这种专门知识，并从航天飞机技术中受益，以推动T细胞研究的发展。该项目有两个主要目标：1-优化基于穿梭机的货物转移方法到培养中的T细胞核; 2-提供T细胞中基因编辑的原理验证。这项工作将使Feldan和Delisle实验室能够获得关键数据，以利用额外的资金来实现将航天飞机技术定位在不断扩大的T细胞编辑领域的目标。

Recent advances in biotechnology allow for the genetic modification of animal and human cells forapplications in research and medicine. This field is extremely promising and is likely to change how research isperformed and how therapies are designed in the future, notably by using cells as medicines. This might beespecially true for T cells, a subset of immune cells capable to fight refractory infections and certain cancers.This project matches a novel approach to genetically engineer cells (developed by Feldan, a biotechnologycompany) with the T-cell handling expertise developed at the University of Montréal. Specifically, theprincipal objective of this application is to develop and validate the best method to genetically engineer T cellsusing a Feldan product; the Shuttle. The Shuttle allows for the delivery of a cargo within the nucleus of the cell,where the genetic material is located. This transport is non-traumatic to the cell and as such may represent amarked advantage compared to competing approaches in the field. We will thus use the Shuttle to carryproteins capable to precisely modify the genetic code of cells (commonly referred as the CRISPR/Cas9system). Although the Shuttle can be used to genetically engineer several cell types, Feldan has no experienceusing it in T cells. The Delisle laboratory at the University of Montréal will provide this expertise and benefitfrom the Shuttle technology to advance the development of T-cell research. The project has two main aims;1-to optimize Shuttle-based cargo transfer methods to the nucleus of T cells in culture and 2- to provide aproof-of-principle of genetic editing in T cells. This work will enable Feldan and the Delisle laboratory toobtain key data to leverage additional funding towards the goal of positioning the Shuttle technology in theexpanding field of T-cell editing.