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AAV vectors trigger neurotoxic DNA damage responses and STING-dependent inflammation in human CNS cells [scRNAseq_dataset2]

GSE253822 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2025/03/11 Platform GPL18573
Summary
Adeno-associated viral (AAV) vector gene therapy is gaining ground as a treatment option for genetic neurodegenerative diseases tha currently have no cure. Nonetheless, significant toxicity and severe adverse events are emerging in recent clinical trials through mechanisms that remain unclear. We have modelled here AAV-mediated neurotoxicity in the context of the human brain taking advantage of human induced pluripotent stem cell-based technologies. We have used single-cell RNA sequencing technologies to interrogate vector-induced cell-intrinsic innate immune mechanisms that could contribute to neurotoxicity in 3D brain sphheroids transduced with AAV vectors at different time-points and harvested at two different time-points.
Published in
AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain
Costa-Verdera H, Meneghini V, Fitzpatrick Z et al. · Nature communications 2025 · PMID 40251179 · doi:10.1038/s41467-025-58778-3
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Direct links to NCBI, no account and no request form: the whole study as GSE253822_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1067334 and SRA study SRP485047. Searching any of these in the dataset finder brings you back here.

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