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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

This is our proudest work yet—a blueprint for rationally designing next-generation cell therapies. Data and methods are fully open-source for academic use and licensable for translation. Out in @nature.com today. www.nature.com/articles/s41...

nature.com

Systematic discovery of CRISPR-boosted CAR T cell immunotherapies - Nature

CELLFIE, a CRISPR platform for optimizing cell-based immunotherapies, identifies gene knockouts that enhance CAR T cell efficacy using in vitro and in vivo screens.

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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

Great teamwork: P Datlinger*✉️, E Pankevich*, C Arnold*, N Pranckevicius, J Lin, D Romanovskaia, M Schäfer, F Piras, AC Orts, A Nemc, P Biesaga, M Chan, T Neuwirth, A Artemov, W Li, S Ladstätter, T Krausgruber & C Bock✉️ (*first authors, ✉️correspondance).

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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

CELLFIE supports diverse CRISPR modalities. Base editing proved especially powerful. Tiling screens of RHOG suggest inhibition of GTP binding pocket as therapeutic angle and identified gRNAs for clinical translation. (7/7)

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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

With many promising single edits reported across labs, the key challenge is combining them into tailored therapeutic designs. We extended CELLFIE with combinatorial screens and discovered a strong synergy between RHOG and FAS knockouts. (6/7)

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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

RHOG was a surprising hit and has been linked to immunodeficiency in humans. Yet in CAR T cells, RHOG knockout drives proliferation, fosters a central memory phenotype, and reduces exhaustion. (5/7)

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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

We developed in vivo CROP-seq for screens in mouse immunotherapy models. By reading gRNAs from abundant mRNA and tracking individual clones, we identified RHOG, FAS, and PRDM1 as CAR T boosters. In vivo CROP-seq supports discovery screens with thousands of perturbations. (4/7)

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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

To address clinical limitations of CAR T therapies, we performed genome-scale FACS screens for target recognition, T cell activation, apoptosis/fratricide, and exhaustion—resulting in the largest CAR T screening dataset to date. (3/7)

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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

We ran genome-wide screens for T cell fitness under TCR and repeated target cell stimulation. This revealed novel knockouts that enhance CAR T cell persistence, alongside many well-known clinical targets. (2/7)

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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

#CELLFIE for CAR T screening—a new mRNA-based platform for screening primary cells. CAR + gRNA library are delivered by lentivirus, CRISPR modifiers as electroporated mRNA. That’s more flexible and effective than existing T cell screening methods. (1/7)

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pauldatlinger.bsky.social @pauldatlinger.bsky.social · 24/09/2025

CAR T cells showcase the enormous potential of cell therapies, but often fail due to lack of evolutionary optimization. Today in @nature.com , we use #CELLFIE to engineer cell therapies at scale and share the largest resource of CRISPR screens in CAR T cells. www.nature.com/articles/s41...

nature.com

Systematic discovery of CRISPR-boosted CAR T cell immunotherapies - Nature

CELLFIE, a CRISPR platform for optimizing cell-based immunotherapies, identifies gene knockouts that enhance CAR T cell efficacy using in vitro and in vivo screens.

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