Show Notes
StealTHY CRISPR: Revealing Hidden Metastasis Regulators
Music:
Enjoy the music based on this article at the end of the episode.
License:
CC BY 4.0 International License (CC BY 4.0)
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Episode link: https://basebybase.com/episodes/stealthy-crispr-revealing-hidden-metastasis-regulators
️ Episode:
204: StealTHY CRISPR: Revealing Hidden Metastasis Regulators
️ Season:
1
Article title:
Stealthy CRISPR: Revealing Hidden Metastasis Regulators
Journal:
Cell
DOI:
10.1016/j.cell.2025.10.007
QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-11-20.
QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript sections describing: CRISPR immunogenicity in vivo, design of the stealthy platform (immune stealth reporters, Hit-and-Run Cas9, Harakiri selection), ex vivo purification, preservation of library diversity in immunocompetent models, identification and magnitude of AMHR2 axis in metastasis, transl
- transcript topics: CRISPR immunogenicity in vivo; Stealthy platform design: immune stealth reporters, autologous reporters, hit-and-run Cas9, transient Cas9 delivery; Harakiri selection and ex vivo purification; Preservation of sgRNA library diversity in immunocompetent models; AMHR2 axis as metastasis driver and magnitude of effect; Clinical relevance: TCGA correlation, prognosis in breast cancer
QC Summary:
- factual score: 10/10
- metadata score: 4/10
- supported core claims: 8
- claims flagged for review: 0
- metadata checks passed: 1
- metadata issues found: 3
Metadata Audited:
- article_doi
- article_title
- article_journal
- license
Factual Items Audited:
- Stealthy CRISPR platform uses immune stealth reporters, HiT-and-Run delivery, and Harakiri selection to render CRISPR screens immunologically inert in vivo
- In immunocompetent models, stealthy platform preserves clonal diversity and full SGRNA library integrity, unlike CAST9-based controls which collapse diversity
- AMHR2 axis identified as a major driver of metastasis; knockout yields a 20-fold reduction in metastases
- Dominant negative AMHR2 decoy receptor suppresses tumor volume by >80% and essentially abolishes metastasis in humanized/PDX models
- Blocking AMHR2 signaling shifts tumor immune microenvironment: reduced Tregs, increased activated macrophages and cytotoxic T cells; Type I interferon genes and STAT1 pathway are e
- Human relevance supported via TCGA data showing high AMH expression correlates with poor prognosis in breast cancer
Internal QC note: metadata cleanup is still recommended before publication.
QC result: Warning. Review the flagged items before publication.
