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基因改造，使其在研究和医学中得到应用。这一领域非常有前景，很可能改变未来进行研究和设计疗法的方式，特别是通过将细胞用作药物。T细胞尤其如此，T细胞是免疫细胞的一个子集，能够对抗难治性感染和某些癌症。该项目将一种新的细胞遗传工程方法(由生物技术公司Feldan开发)与蒙雷亚尔大学开发的T细胞处理专业知识相匹配。具体地说，这项应用的主要目标是开发和验证使用费尔登产品-航天飞机-对T细胞进行基因工程的最佳方法。航天飞机允许在遗传物质所在的细胞核内运送货物。这种传输对细胞是非创伤性的，因此与该领域的竞争方法相比可能具有显著的优势。因此，我们将使用航天飞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)。尽管航天飞机可以用来对几种类型的细胞进行基因工程，但费尔丹没有在T细胞上使用它的经验。蒙特雷亚尔大学的Delisle实验室将提供这方面的专业知识，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-优化基于航天飞机的货物在培养中转移到T细胞核的方法；2-提供T细胞基因编辑的原理证据。这项工作将使Feldan和Delisle实验室能够获得关键数据，以利用额外的资金实现将Shuttle技术定位于不断扩大的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.