A revolutionary cell programming platform based on the targeted nano-delivery of a transposon gene editing system

Project Information

NANO-ENGINE

Grant agreement ID: 101098944

DOI

10.3030/101098944

EC signature date 15 March 2023

Start date 1 April 2023

End date 31 July 2026

Funded under

• The European Innovation Council (EIC)

Total cost

€ 2 988 377,95

EU contribution

€ 2 988 377,70

Coordinated by

UNIVERSITEIT UTRECHT
Netherlands

Periodic Reporting for period 1 - NANO-ENGINE (A revolutionary cell programming platform based on the targeted nano-deliveryof a transposon gene editing system)

Reporting period: 2023-04-01 to 2024-03-31

Summary of the context and overall objectives of the project

Chimeric antigen receptor (CAR) T-cell therapy represents a groundbreaking advance in cancer treatment, fundamentally changing the approach to managing previously intractable forms of blood cancers, such as certain leukemias and lymphomas. This innovative therapy involves genetically modifying a patient's T cells ex vivo to express a CAR that targets specific antigens on tumor cells, enabling the immune system to better recognize and destroy cancer cells. The results have been transformative, particularly for patients who have exhausted other treatment options, showing remarkable success rates in clinical trials. However, CAR T-cell therapy is not without its downsides. The treatment is highly specialized and expensive, limiting access to a broader patient population. In addition, the T cells run the risk of premature exhaustion due to the intensive culturing schedule.
The overall aim of the NANO-ENGINE project is to establish PoC for the first in vivo cell engineering platform technology by demonstrating efficient in vivo transfection of T cells and preliminary efficacy in treatment of CD19+ B cell malignancies.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We have successfully generated the four components of our targeted nanoparticle and have shown that the nanoparticle can be assembled selectively target T cells and transfect them. We have set up QC measures to evaluate the critical quality attributes of our targeted nanoparticle.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Task 1.6 was performed ahead of schedule. To the best of our knowledge the presented transfection levels (60 -70%) are in a great excess of reported levels of non-viral DNA transfection of T cells in literature. These results need to be validated in vivo to ensure further uptake and success.