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.