450: ASOs que reduzem PrP prolongam a sobrevida [PT]

Raymond GJ et al., JCI Insight - This episode covers a 2019 study showing that sequence-specific antisense oligonucleotides (ASOs) targeting the prion protein (PrP) mRNA, delivered by bolus intracerebroventricular injection, lower PrP levels in the CNS, slow neuropathology, and markedly extend survival in prion-infected wild-type mice when given prophylactically or even near symptom onset. Key terms: antisense oligonucleotide, prion disease, prion protein, intracerebroventricular, mouse model. Study Highlights:Two PrP-targeting ASOs (active ASO 1 and 2) reduced Prnp mRNA and PrP protein across brain regions and produced robust survival benefits in RML prion–infected wild-type mice, with prophylactic extension of lifespan by 61%–98%. A single bolus dose given at 120 days post-infection (near clinical onset) extended survival by 55% and slowed symptomatic progression. A non‑targeting control ASO showed no efficacy, indicating a sequence-specific, on‑target mechanism mediated by RNase H–dependent RNA lowering. Some tolerability issues were observed with particular ASO candidates at late-stage treatment, but at least one active ASO was both tolerated and effective. Conclusion:Bolus CNS delivery of sequence-specific PrP‑lowering ASOs lowers PrP, delays prion neuropathology, and substantially extends survival in infected mice, supporting further development of PrP‑lowering therapy and use of CSF PrP as a pharmacodynamic biomarker. Music:Enjoy the music based on this article at the end of the episode. Article title:Antisense oligonucleotides extend survival of prion-infected mice First author:Raymond GJ Journal:JCI Insight DOI:10.1172/jci.insight.131175 Reference:Raymond GJ, Zhao HT, Race B, et al. Antisense oligonucleotides extend survival of prion-infected mice. JCI Insight. 2019;4(16):e131175. doi:10.1172/jci.insight.131175. License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at 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/450-prp-lowering-asos-prion-mice QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-08-24. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited sections describing ASOs targeting Prnp, PrP reduction, i.c.v. bolus delivery, prophylactic vs late-stage treatment in prion-infected mice, and the role of control ASOs and sequence specificity.- transcript topics: Antisense oligonucleotides targeting Prnp mRNA; PrP reduction and PrP biology; Intracerebroventricular bolus delivery vs continuous infusion; Prophylactic vs late-stage treatment in prion-infected mice; Sequence specificity and non-targeting control ASO; Pharmacodynamic biomarker: CSF PrP measurement QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 6- 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:- ASOs targeting Prnp mRNA discussed as a therap...