NOn-VIral gene modified STEM cell therapy

1 November 2022 - 31 October 2026

Diagnosis & treatmentEuropean Research Council (ERC)Horizon Europe2022

NOVISTEM project aims to streamline the genetic modification of iPSCs and their subsequent use in cell therapy.

Project description

Despite the increasing awareness that cell and gene-therapy approaches have tremendous biomedical potential, their broad clinical application has been challenging due to prolonged and expensive production times and the emergence of severe immune- and gene-delivery dependent side effects.

In this proposal, we aim to establish a stream-lined and high-throughput protocol for iPSC-based cell therapy by combining a novel technological platform for gene delivery with a breakthrough biological concept that will permit to manufacture functional, gene-corrected blood forming stem cells and CAR T cells.

To achieve this, we will use and optimize photoporation as non-viral gene delivery method for CRISPR-mediated and site-specific gene-editing to obtain controlled CAR expression and for performing gene-correction in iPSCs. From these gene-modified iPSCs, we will generate CAR T cells and blood forming stem cells, respectively, by selectively targeting a signaling pathway that we established to be critical in human blood cell development and particularly T cell development.

Following functional validation of the generated cell products, we will optimize the current protocols to increase the potential for clinical implementation and establish a high-throughput photoporation platform to generate a large number of CAR expressing iPSC lines from different ages, sex and ethnicities to demonstrate the population-wide implementation potential of our approach. This will allow to generate a bank of well-characterized, HLA-defined CAR expressing iPSC that can be used as of-the-shelf cell therapy products. Thereby significantly advancing the currently implemented adaptive CAR T cell approaches by reducing the production costs and time, by selectively targeting the CAR into a well-controlled location which will prevent variability and by facilitating the production and evaluation of novel CARs for other cancer entities such as solid tumors.

Funding programme & Type of action

Funding programme : Horizon Europe – European Innovation Council (EIC)
Type of action : HORIZON EIC Grants
Grant agreement number : 101071105

Belgian partners

Universiteit Gent (Ugent)


4 years