Novel approach for T-cell genetic editing

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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.