204: StealTHY CRISPR: Revealing Hidden Metastasis Regulators

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) Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. 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 transcript sections describing stealth platform design, immunogenicity challenges in vivo, iatrogenic clonal dropout, Harakiri purification, AMHR2 axis as a metastasis driver, and translational relevance via TCGA. - transcript topics: CRISPR immunogenicity in vivo and iatrogenic clonal dropout; Stealth platform design: immune stealth reporters, autologous reporters, Hit-and-Run Cas9; Harakiri selection and ex vivo purification; Preservation of sgRNA library diversity in immunocompetent models; AMHR2 axis as metastasis driver; Dominant negative AMHR2 decoy receptor therapy in humanized/PDX models QC Summary: - factual score: 10/10 - metadata score: 10/10 - supported core claims: 7 - claims flagged for review: 0 - metadata checks passed: 4 - metadata issues found: 0 Metadata Audited: - article_doi - article_title - article_journal - license Factual Items Audited: - Stealth CRISPR platform uses immune stealth reporters, HiT-and-Run Cas9 delivery, and Harakiri selection to render CRISPR screens immunologically inert - In immunocompetent models, stealth platform preserves clonal diversity and full sgRNA library integrity - 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 upreg - Human relevance supported via TCGA data showing high AMH expression correlates with poor prognosis in breast cancer QC result: Pass.