GEO series
Dynamic activation of rAAV transgene expression by a small molecule that recruits endogenous transcriptional machinery
GSE272562
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing
46 samples
Submitted 2025/04/08
Platform GPL30173Platform GPL30882
Summary
The silencing of adeno-associated virus (AAV) vectors over time poses a challenge to the development of effective gene therapies. Here, we describe a bioorthogonal platform for tuning AAV expression, enabling the controlled activation of viral transgenes after transduction. This platform uses a small, synthetic DNA binding protein embedded in the AAV genome coupled with a heterobifunctional small molecule that recruits endogenous transcriptional machinery to chemically induce transgene expression in a dose-dependent and reversible manner. In human cells, this strategy successfully activates AAV expression across different viral serotypes, cassette configurations, and transgene payloads. Epigenomic analysis reveals that this technology facilitates direct and specific recruitment of the transcriptional regulator BRD4 to AAV genomes. Our results demonstrate that the expression of native AAV genomes can be tuned through chemically induced proximity (CIP), opening the possibility of a new class of AAV vectors that can be dynamically potentiated.
Published in
Wasserman SR, Muron S, Lee HR et al.
· Nucleic acids research 2025
· PMID 40298110
· doi:10.1093/nar/gkaf345
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE272562_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 46 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1137350 and SRA study SRP520807. Searching any of these in the dataset finder brings you back here.
Study design
11 conditions, mostly with about 4 replicates each
U2OS BRD4 no treatment ×4
U2OS BRD4 C207 treatment ×4
U2OS H3K9ac no treatment ×4
U2OS H3K9ac C207 treatment ×4
U2OS H3K27ac no treatment ×4
U2OS H3K27ac C207 treatment ×4
U2OS cells, no infection, DMSO, ×4
U2OS cells, no infection, 300 nM C207, ×4
+4 more
Supports a between-group comparison across 39 samples.
11 replicated groups read from the first 40 of 46 sample titles; they account for 39 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8404607 U2OS BRD4 no treatment Rep1
- GSM8404608 U2OS BRD4 no treatment Rep2
- GSM8404609 U2OS BRD4 no treatment Rep3
- GSM8404610 U2OS BRD4 no treatment Rep4
- GSM8404611 U2OS BRD4 C207 treatment Rep1
- GSM8404612 U2OS BRD4 C207 treatment Rep2
- GSM8404613 U2OS BRD4 C207 treatment Rep3
- GSM8404614 U2OS BRD4 C207 treatment Rep4
- GSM8404615 U2OS H3K9ac no treatment Rep1
- GSM8404616 U2OS H3K9ac no treatment Rep2
- GSM8404617 U2OS H3K9ac no treatment Rep3
- GSM8404618 U2OS H3K9ac no treatment Rep4
- GSM8404619 U2OS H3K9ac C207 treatment Rep1
- GSM8404620 U2OS H3K9ac C207 treatment Rep2
- GSM8404621 U2OS H3K9ac C207 treatment Rep3
- GSM8404622 U2OS H3K9ac C207 treatment Rep4
- GSM8404623 U2OS H3K27ac no treatment Rep1
- GSM8404624 U2OS H3K27ac no treatment Rep2
- GSM8404625 U2OS H3K27ac no treatment Rep3
- GSM8404626 U2OS H3K27ac no treatment Rep4
- GSM8404627 U2OS H3K27ac C207 treatment Rep1
- GSM8404628 U2OS H3K27ac C207 treatment Rep2
- GSM8404629 U2OS H3K27ac C207 treatment Rep3
- GSM8404630 U2OS H3K27ac C207 treatment Rep4
- GSM8404631 U2OS IgG no treatment Rep1
- GSM8404632 U2OS IgG no treatment Rep2
- GSM8404633 U2OS IgG no treatment Rep3
- GSM8404634 U2OS IgG C207 treatment Rep1
- GSM8404635 U2OS IgG C207 treatment Rep2
- GSM8404636 U2OS IgG C207 treatment Rep3a
- GSM8833011 U2OS cells, no infection, DMSO, biological replicate 1
- GSM8833012 U2OS cells, no infection, DMSO, biological replicate 2
- GSM8833013 U2OS cells, no infection, DMSO, biological replicate 3
- GSM8833014 U2OS cells, no infection, DMSO, biological replicate 4
- GSM8833015 U2OS cells, no infection, 300 nM C207, biological replicate 1
- GSM8833016 U2OS cells, no infection, 300 nM C207, biological replicate 2
- GSM8833017 U2OS cells, no infection, 300 nM C207, biological replicate 3
- GSM8833018 U2OS cells, no infection, 300 nM C207, biological replicate 4
- GSM8833019 U2OS cells, 10k vg/cell AAV2 Jet-FKBP*, 300 nM C207, biological replicate 1
- GSM8833020 U2OS cells, 10k vg/cell AAV2 Jet-FKBP*, 300 nM C207, biological replicate 2
+ 6 more — browse all 46 samples with per-sample file links →
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