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In vivo gene editing of human hematopoietic stem and progenitor cells using envelope-engineered virus-like particles (PHH cells)

GSE267282 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2025/12/17 Platform GPL20301
Summary
Engineered virus-like particles (VLPs) are a promising technology for in vivo gene editing of human hematopoietic stem and progenitor cells (HSPCs). Here we design and test two different VLP envelopes for human HSPC editing in vitro and in vivo. The first is an optimized version of the baboon envelope BaEVTR, which efficiently transduces human HSPCs in vitro. We show that the optimized BaEVTR VLP enables in vivo editing of β2 microglobulin in long-term human HSPCs (31% at 8 weeks after dosing) and editing of two hemoglobinopathy-relevant loci, BCL11A and HBG1/2 (26% and 7.5%, respectively, at 5 days after dosing), inducing fetal hemoglobin. Our second VLP design uses a CD133-targeted envelope designed to reduce the transduction of mature blood cells and achieves higher in vivo specificity for HSPCs compared to the optimized BaEVTR VLP. As avoiding delivery in filter organs such as the liver would enhance efficiency and safety, we also demonstrate that both VLPs avoid human hepatocytes in a humanized liver model.
Published in
In vivo gene editing of human hematopoietic stem and progenitor cells using envelope-engineered virus-like particles
Botchkarev VV Jr, Harrington S, Stoppato M et al. · Nature biotechnology 2025 · PMID 41350944 · doi:10.1038/s41587-025-02915-2
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Also filed as BioProject PRJNA1110981 and SRA study SRP507295. Searching any of these in the dataset finder brings you back here.

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