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iRNA|CAR-T: An All-RNA Platform for Durable In Vivo Generation of Cancer-Specific CAR-T Cells

Objective

I propose iRNA|CAR-T (integrating RNA-mediated CAR-T), a next-generation platform for the in vivo creation of chimeric antigen receptor (CAR) T cells using all-RNA genome editors delivered by lipid nanoparticles (LNPs). This approach directly addresses key limitations of current CAR-T therapies—complex ex vivo manufacturing and toxic lymphodepleting chemotherapy—by enabling CAR-T generation within the patient’s body, thereby simplifying manufacture, broadening patient access, and reducing treatment-related burden. Focusing initially on CD19-directed CARs for B-cell malignancies, iRNA|CAR-T will establish a scalable in vivo CAR-T production platform, that is generalizable to all CAR-T indications.

iRNA|CAR-T combines two all-RNA DNA-writing systems: R2 retrotransposons for inserting large gene fragments into genomic safe-harbour sites, and CRISPR prime editing (PE) for precise sequence modifications at the nucleotide level. Together, they transform transient RNA delivery into lasting genomic modifications enabling stable CAR integration, durable CAR-expression, and sustained CAR-T activity as well as selective expansion of CAR-T cells. To enable in vivo application, I will employ LNPs—a clinically proven and scalable system for selective T cell delivery. Integrating LNPs with all-RNA DNA-writing tools establishes a fully RNA-based strategy for in vivo T cell engineering, enabling clinically-scalable in vivo CAR-T generation.

During my postdoc, I provided the first demonstration of PE in primary human T cells gaining expertise in translating cutting-edge genome engineering technologies to primary T cell systems. I will leverage this expertise to develop the iRNA|CAR-T platform for in vivo CAR-T production. Its simplicity and scalability will expand CAR-T therapy to new indications and, more broadly, establish a platform for in vivo gene editing and addition applicable to a wide range of genetic diseases.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2026-STG

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Host institution

UNIVERSITAETSKLINIKUM WUERZBURG - KLINIKUM DER BAYERISCHEN JULIUS-MAXIMILIANS-UNIVERSITAT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 438 085,00
Address
JOSEF-SCHNEIDER-STRASSE 2
97080 WURZBURG
Germany

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Region
Berlin Berlin Berlin
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 438 085,00

Beneficiaries (1)