{"version":1,"type":"rich","provider_name":"Libsyn","provider_url":"https:\/\/www.libsyn.com","height":90,"width":600,"title":"Podcast 993: Personalized Gene Editing Therapy","description":"Contributor: Alec Coston, MD Educational Pearls: Disclaimer: this has nothing to do with the ER but is too cool to not talk about. Condition: Carbamoyl phosphate synthetase 1 (CPS1) deficiency Rare inborn error of metabolism Inability to properly break down ammonia Leads to severe hyperammonemia and hepatic encephalopathy Natural history: Without treatment, typically fatal within the first few weeks of life Even with current standard treatments, life expectancy is often limited to ~5\u20136 years Breakthrough treatment: A team of researchers at the Children\u2019s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania developed the CRISPR-based targeted gene therapy for this patient. First-of-its-kind precision approach tailored to the patient\u2019s specific mutation Key components of the therapy: Whole-genome sequencing to identify the exact CPS1 mutation Creation of a custom base-editing enzyme designed to correct that specific mutation Design of a guide RNA to direct the base editor to the precise genomic location Delivery method: Lipid nanoparticles used to deliver the gene-editing machinery Nanoparticles can be targeted to specific tissues Why the liver works well: CPS1 is primarily expressed in hepatocytes The liver is relatively easy to target with lipid nanoparticles Hepatocytes divide frequently, allowing edited genes to be passed on as cells replicate Long-term impact: Once edited, cells continue producing functional CPS1 enzyme Potential for durable, possibly lifelong correction from a single treatment References https:\/\/www.nih.gov\/news-events\/news-releases\/infant-rare-incurable-disease-first-successfully-receive-personalized-gene-therapy-treatment Choi Y, Oh A, Lee Y, Kim GH, Choi JH, Yoo HW, Lee BH. Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency. Clin Chim Acta. 2022 Feb 1;526:55-61. doi: 10.1016\/j.cca.2021.11.029. Epub 2021 Dec 29. PMID: 34973183. Bharti N, Modi U, Bhatia D, Solanki R. Engineering delivery platforms for CRISPR-Cas and their applications in healthcare, agriculture and beyond. Nanoscale Adv. 2026 Jan 5. doi: 10.1039\/d5na00535c. Epub ahead of print. PMID: 41640466; PMCID: PMC12865601. Summarized and edited by Jeffrey Olson MS4 Donate: https:\/\/emergencymedicalminute.org\/donate\/ Join our mailing list: http:\/\/eepurl.com\/c9ouHf ","author_name":"Emergency Medical Minute","author_url":"https:\/\/www.emergencymedicalminute.com","html":"