GEO series

Quadruple adenine base edited allogeneic CAR T cells outperform CRISPR/Cas9 nuclease engineered T cells [RNA-seq]

GSE290621 Homo sapiens (human) RNA-seq (gene expression) 33 samples Submitted 2025/04/09 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 33 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 33 samples: 33 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Genome editing technologies have enabled the clinical development of allogeneic cellular therapies, yet the optimal gene editing modality for multiplex editing of therapeutic T cell product manufacturing remains elusive. In this study, we conducted a comprehensive comparison of CRISPR/Cas9 nuclease and adenine base editor (ABE) technologies in generating allogeneic chimeric antigen receptor (CAR) T cells, utilizing extensive in vitro and in vivo analyses.

Read the full summary ↓

Both methods achieved high editing efficiencies across four target genes, critical for mitigating graft-versus-host disease and allograft rejection: TRAC or CD3E, B2M, CIITA, and PVR. Notably, ABE demonstrated higher manufacturing yields and distinct off-target profiles compared to Cas9, with translocations observed exclusively in Cas9-edited products. Functionally, ABE-edited CAR T cells exhibited superior in vitro effector functions under continuous antigen stimulation, including enhanced proliferative capacity and increased surface CAR expression. Transcriptomic analysis revealed that ABE editing resulted in reduced activation of p53 and DNA damage response pathways at baseline, along with sustained activation of metabolic pathways during antigen stress. Consistently, ATAC-seq data indicated that Cas9-edited, but not ABE-edited, CAR T cells showed enrichment of chromatin accessibility peaks associated with double-strand break repair and DNA damage response pathways. In a preclinical leukemia model, ABE-edited CAR T cells demonstrated improved tumor control and extended overall survival compared to their Cas9-edited counterparts. Collectively, these findings position ABE as a superior choice of Cas9 nucleases for multiplex gene editing in therapeutic T cells.

This dataset

Open GSE290621 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE290621_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1229426 and SRA study SRP566929. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

33 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 33 sample titles: 33 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8818293 UTD T cells, No EP, D0, donor ND502, RNA-seq
GSM8818294 CTL019 CAR T cells, No EP, D0, ND502, RNA-seq
GSM8818295 CTL019 CAR T cells, No EP, End of CAE, ND502, RNA-seq
GSM8818296 CTL019 CAR T cells, ABE mRNA 4KO, D0, ND502, RNA-seq
GSM8818297 CTL019 CAR T cells, ABE mRNA 4KO, End of CAE, ND502, RNA-seq
GSM8818298 CTL019 CAR T cells, Cas9 WT mRNA 4KO, D0, ND502, RNA-seq
GSM8818299 CTL019 CAR T cells, Cas9 WT mRNA 4KO, End of CAE, ND502, RNA-seq
GSM8818300 CTL019 CAR T cells, Cas9 SpyFi mRNA 4KO, D0, ND502, RNA-seq
GSM8818301 CTL019 CAR T cells, Cas9 SpyFi mRNA 4KO, End of CAE, ND502, RNA-seq
GSM8818302 CTL019 CAR T cells, Cas9 SpyFi Protein 4KO, D0, ND502, RNA-seq
GSM8818303 CTL019 CAR T cells, Cas9 SpyFi Protein 4KO, End of CAE, ND502, RNA-seq
GSM8818304 UTD T cells, No EP, D0, donor ND541, RNA-seq
GSM8818305 CTL019 CAR T cells, No EP, D0, ND541, RNA-seq
GSM8818306 CTL019 CAR T cells, No EP, En of CAE, ND541, RNA-seq
GSM8818307 CTL019 CAR T cells, ABE mRNA 4KO, D0, ND541, RNA-seq
GSM8818308 CTL019 CAR T cells, ABE mRNA 4KO, End of CAE, ND541, RNA-seq
GSM8818309 CTL019 CAR T cells, Cas9 WT mRNA 4KO, D0, ND541, RNA-seq
GSM8818310 CTL019 CAR T cells, Cas9 WT mRNA 4KO, End of CAE, ND541, RNA-seq
GSM8818311 CTL019 CAR T cells, Cas9 SpyFi mRNA 4KO, D0, ND541, RNA-seq
GSM8818312 CTL019 CAR T cells, Cas9 SpyFi mRNA 4KO, End of CAE, ND541, RNA-seq
GSM8818313 CTL019 CAR T cells, Cas9 SpyFi Protein 4KO, D0, ND541, RNA-seq
GSM8818314 CTL019 CAR T cells, Cas9 SpyFi Protein 4KO, End of CAE, ND541, RNA-seq
GSM8818315 UTD T cells, No EP, D0, donor ND602, RNA-seq
GSM8818316 CTL019 CAR T cells, No EP, D0, ND602, RNA-seq
GSM8818317 CTL019 CAR T cells, No EP, En of CAE, ND602, RNA-seq
GSM8818318 CTL019 CAR T cells, ABE mRNA 4KO, D0, ND602, RNA-seq
GSM8818319 CTL019 CAR T cells, ABE mRNA 4KO, End of CAE, ND602, RNA-seq
GSM8818320 CTL019 CAR T cells, Cas9 WT mRNA 4KO, D0, ND602, RNA-seq
GSM8818321 CTL019 CAR T cells, Cas9 WT mRNA 4KO, End of CAE, ND602, RNA-seq
GSM8818322 CTL019 CAR T cells, Cas9 SpyFi mRNA 4KO, D0, ND602, RNA-seq
GSM8818323 CTL019 CAR T cells, Cas9 SpyFi mRNA 4KO, End of CAE, ND602, RNA-seq
GSM8818324 CTL019 CAR T cells, Cas9 SpyFi Protein 4KO, D0, ND602, RNA-seq
GSM8818325 CTL019 CAR T cells, Cas9 SpyFi Protein 4KO, End of CAE, ND602, RNA-seq

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