Show Notes
Geilenkeuser J et al., Cell - A Cell paper describing ENVLPE/ENVLPE+, virus-like particles engineered with nucleocytosolic-shuttling Gag-PCP to recruit aptamer-tagged (pe)gRNAs and preferentially package fully assembled CRISPR RNPs. Csy4-mediated 3' protection of pegRNAs and modular minimal budding modules boost prime and base editing in cells and restore gene function in retinal mouse models. Key terms: VLP, prime editing, pegRNA stabilization, Csy4, gene delivery.
Study Highlights:
The authors engineered nucleocytosolic-shuttling Gag-PCP VLPs (ENVLPE) that retrieve assembled Cas effector RNPs via PP7-aptamer-tagged (pe)gRNAs, increasing the fraction of functional cargo. Co-expression of Csy4 stabilizes pegRNA 3' ends and markedly improves prime editing rates during RNP delivery. A minimal homomeric “miniENVLPE” and an enhanced ENVLPE+ with GCN4 coiled coils achieve high per-particle loading of Cas9 and pegRNA. ENVLPE+ outperforms prior eVLP systems ex vivo in primary T cells and in vivo in two mouse retinal disease models, restoring protein expression and visual function.
Conclusion:
ENVLPE+ is a modular VLP platform that preferentially packages intact RNP editors via aptamer-tagged (pe)gRNAs and uses Csy4 to protect pegRNA 3' ends, producing higher per-particle editing efficiency and demonstrating therapeutic potential in ex vivo and in vivo models.
QC:
This episode was checked against the original article PDF and publication metadata.
Scope: article metadata and core scientific claims from the narration, excluding analogies, intro/outro, and music.
Factual QC score: 10/10.
Metadata QC score: 10/10.
Supported core claims: 8.
Claims flagged for review: 0.
Metadata checks passed: 4.
Metadata issues found: 0.
QC result: Pass.
Music:
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Article title:
Engineered nucleocytosolic vehicles for loading of programmable editors
First author:
Geilenkeuser J
Journal:
Cell
DOI:
10.1016/j.cell.2025.03.015
Reference:
Geilenkeuser J., Armbrust N., Steinmaßl E., et al. Engineered nucleocytosolic vehicles for loading of programmable editors. Cell. 2025;188:2637–2655. https://doi.org/10.1016/j.cell.2025.03.015
License:
CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/)
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