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Reposted by Dimitrios L. Wagner

bioRxiv Immunology @biorxiv-immuno.bsky.social · 1d

TCR activation impairs CAR-T cytotoxicity against separate target cells https://www.biorxiv.org/content/10.1101/2025.10.07.680634v1

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Reposted by Dimitrios L. Wagner

DL Wagner Genome Engineering Labs @dlwagnerlabs.bsky.social · 3d

Our team is on their way to the ESGCT conference 2025! Excited for this upcoming week full of science, talks, and inspiring discussions with the cell & gene therapy community!
Starting with the HDR workshop - talks by Isabell (‘one-pot’ PASTA) & Viktor
(BEKI) + posters by Ana, Lily, Jonas and Laura

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Reposted by Dimitrios L. Wagner

Lorenz Bastian @lbastianmd.bsky.social · 10d

Excited to share our preprint📯:
We introduce #IntegrateALL, an open-source RNA-seq pipeline for interpretable molecular diagnostics in acute lymphoblastic leukemia!🧬
Big thanks to Nadine Wolgast & team @ www.uksh.de
, catchall-kfo5010.com!
See: doi.org/p7k5 and 🧵

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Reposted by Dimitrios L. Wagner

Lorenz Bastian @lbastianmd.bsky.social · 10d

Big shoutout to the whole group who made #IntegrateALL possible - especially @alinamh.bsky.social, Thomas Beder and Claudia Baldus at www.catchall-kfo5010.com

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Reposted by Dimitrios L. Wagner

bioRxiv Immunology @biorxiv-immuno.bsky.social · 13d

Potentiating CAR-T bystander killing by enhanced Fas/FasL signaling mitigates antigen escape in heterogeneous tumors https://www.biorxiv.org/content/10.1101/2025.09.22.677496v1

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Reposted by Dimitrios L. Wagner

Laura Hartmann @lmhartmann.bsky.social · 15d

Check out one of our latest stories about combining our non viral knock-in strategy with integrases for an efficient, targeted integration of transgenes >8kb in human T cells!

‘One-pot’ PASTA: programmable and site specific transgene addition - all in just one reaction 🫕

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Reposted by Dimitrios L. Wagner

Daniel Ibrahim @danielibrahim.bsky.social · 19d

This has been such a great collaboration with @dlwagnerlabs.bsky.social! You really need to check it out

One-pot PASTA 🍝 - a one-step protocol to knock-in large transgenes.
I feel tempted to think about one-pot PIZZA 🍕 next!

First authors Isabell and @therealjonaskath.bsky.social were amazing!!

Dimitrios L. Wagner @dlwagner.bsky.social · 19d

You like engineering T cells, but you are missing the right flavor?

Check out 'one-pot' PASTA recipe 🔥🍝: www.biorxiv.org/content/10.1101/2025.09.10.675267v1

We combined a unique mix of CRISPR knock-in with serine integrases for easy-to-adopt
𝐏rogrammable
𝐀nd
𝐒ite-specific
𝐓ransgene
𝐀ddition
🧪

Versatile and efficient non-viral integration of large transgenes in human T cells via CRISPR knock-in and engineered integrases

Current gene transfer methods often lack the precision, versatility, or efficiency when integrating large transgenes, limiting the ability to engineer therapeutic T-cells with more complex payloads. H...

www.biorxiv.org

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Reposted by Dimitrios L. Wagner

Jonas Kath @therealjonaskath.bsky.social · 19d

Super-large targeted Knock-Ins in primary T cells, with multigene inserts >8kb, in a single reaction. HOW?? 🙀

Combine simple CRISPR-HDR & Integrases for one-pot PASTA🍝

= Programmable And Site-specific Transgene Addition. 😎

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Dimitrios L. Wagner @dlwagner.bsky.social · 19d

Led by the integrase lover Isabell Kassing (lawyer turned biologist) and our one and only @therealjonaskath.bsky.social. Amazing collab with @danielibrahim.bsky.social who pushed this idea. Lots of help from the @dlwagnerlabs.bsky.social and Alessa Ringel!

❤️

Teamwork GIF

ALT: Teamwork GIF

media.tenor.com

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Dimitrios L. Wagner @dlwagner.bsky.social · 19d

We found that the serine integrase Pa01 can be improved by adding a nucleus localization signal at the c-terminus -a small change that lifts Pa01 en par with the evolved Bxb1 variant from the Liu lab (eeBxb1). Engineered integrases boost 'one-pot' PASTA 🍝🛠️🚀

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Dimitrios L. Wagner @dlwagner.bsky.social · 19d

'one-pot' PASTA is more efficient than non-viral HDR and also better than PASSIGE with large constructs in primary human T cells. 🔬🚀

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Dimitrios L. Wagner @dlwagner.bsky.social · 19d

Super versatile; exchanging just nuclease + template enables you to put your cargo in a different place. 📍🗺️

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Dimitrios L. Wagner @dlwagner.bsky.social · 19d

'one-pot' PASSTA builds on 4 simple reagents that are easy to source & GMP compatible!

1. CRISPR-cas nuclease
2. HDR template (for landing pad insertion)
3. serine integrase mRNA
4. plasmid with cargo

-> a single electroporation in proliferating T cells =
✨ Efficient integration of XL-genes ✨

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Dimitrios L. Wagner @dlwagner.bsky.social · 19d

You like engineering T cells, but you are missing the right flavor?

Check out 'one-pot' PASTA recipe 🔥🍝: www.biorxiv.org/content/10.1101/2025.09.10.675267v1

We combined a unique mix of CRISPR knock-in with serine integrases for easy-to-adopt
𝐏rogrammable
𝐀nd
𝐒ite-specific
𝐓ransgene
𝐀ddition
🧪

Versatile and efficient non-viral integration of large transgenes in human T cells via CRISPR knock-in and engineered integrases

Current gene transfer methods often lack the precision, versatility, or efficiency when integrating large transgenes, limiting the ability to engineer therapeutic T-cells with more complex payloads. H...

www.biorxiv.org

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Dimitrios L. Wagner @dlwagner.bsky.social · 20d

🚀 In preparation for releasing two new stories, @therealjonaskath.bsky.social is revisiting the journey so far—sharing the lab’s last six papers.

What a ride it’s been… 🙌🧬🧪🧫

DL Wagner Genome Engineering Labs @dlwagnerlabs.bsky.social · 21d

Lab History pt. 1
2022 – 🚨 Our first paper is out! 🚨

virus-free CAR knock-in to TRAC locus of primary human T cells with CRISPR-HDR.

➡️ >50% TRAC CD19-CAR T cells through pharmacological modulation

🧬 A key step toward scalable, non-viral CAR-T cell therapies.

DOI: 10.1016/j.omtm.2022.03.018

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Reposted by Dimitrios L. Wagner

Tobias Bexte @bextetobias.bsky.social · 21d

🚨 Paper alert!
"Next-gen multiplex-edited CAR-NK cells: more edits, more power?" @jitc @bmj.com
With @dlwagner.bsky.social we discuss Wang et al.’s landmark paper on multiplex base-edited non-viral CAR-NK cells. Promising efficiency but safety challenges! jitc.bmj.com/content/13/9...

Next-generation multiplex-edited CAR-NK cells: more edits, more power?

First clinical trials demonstrated the safety of adoptive cell transfer with allogeneic natural killer (NK) cell products from healthy donors, making them an attractive candidate for ‘off-the-shelf’ c...

jitc.bmj.com

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Reposted by Dimitrios L. Wagner

immunoboys @immunoboys.bsky.social · 27d

Plasmacytoid dendritic cells can transition to become cDC2s under to influence of TNF, while type-I interferon reduces TNFR expression and thereby inhibits transition. These transitioned cDC2 seem fully functional. 🧪 ⑂

Hornero et al 2025 in Nat Immunol
www.nature.com/articles/s41...

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Reposted by Dimitrios L. Wagner

Ming Tommy Tang @tommytang.bsky.social · Sep 8

23 tools to work with (single-cell) TCR/BCR-seq immune repertoire data 🧵 👇

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Reposted by Dimitrios L. Wagner

John Doench @johndoench.bsky.social · Sep 7

Doomscrolling pause to chat CRISPR libraries! Preprint describes our new, data-driven approach to combine on-target and off-target predictions much more intelligently for *selecting* guides, which we use to develop our newest Cas9 knockout library, Jacquere. Thread: www.biorxiv.org/content/10.1...

Balancing off-target and on-target considerations for optimized Cas9 CRISPR knockout library design

The continued development of high-dimensional CRISPR screen readouts, such as single-cell RNA sequencing and high-content imaging, necessitates compact libraries to enable functional interrogation at ...

www.biorxiv.org

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Reposted by Dimitrios L. Wagner

immunoboys @immunoboys.bsky.social · Sep 6

Horisberger et al separate Lupus nephritis patients in 3 groups by blood:
healthy-like, interferon-dominant and CD8 T cell-dominant.
The CD8 T cell-dominant group had the highest biopsy activity score and highest response rate after 1 year; the healthy-like the most chronic damage. 🧪 ⑂ #NephSky
1/

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Dimitrios L. Wagner @dlwagner.bsky.social · Sep 4

Congrats Juliane!! :) transposable elements are fascinating and so confusing. Hope you can bring some light into the dark with your research. 😊

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Reposted by Dimitrios L. Wagner

immunoboys @immunoboys.bsky.social · Sep 2

A synonymous mitochondrial variant is negatively selected against in short-lived CD8 effectors – How?
The variant changes tRNA pairing from Watson-Crick-Franklin to wobble, thereby reducing translational efficiency in high energy demand. 🧪 ⑂
Lareau et al – 2025
www.pnas.org/doi/10.1073/...

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Reposted by Dimitrios L. Wagner

FOCIS - Federation of Clinical Immunology Societies @focisimmunology.bsky.social · Aug 25

🚨 First-ever FOCIS Journal Club!

🎓 Blood Immunophenotyping Identifies Distinct Kidney Histopathology and Outcomes in Patients with Lupus Nephritis
🗓️ Oct 13 | 🕚 11 AM CT
🎤 Dr. Rao & Dr. Horisberger

💥 FREE for all! (Non-members need code)

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Dimitrios L. Wagner @dlwagner.bsky.social · Aug 22

So accurate, it hurts

Oded Rechavi @odedrechavi.bsky.social · Aug 22

Journals in August

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Reposted by Dimitrios L. Wagner

Oded Rechavi @odedrechavi.bsky.social · Aug 22

Journals in August

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