Episode 3: Kiran Musunuru, gene and base editors hit the clinic and a Bloody Mary mix

Send us Fan MailUPenn's  Kiran Musunuru, a human geneticist and practicing cardiologist who has pioneered the translation of gene- and base-editing approaches, talks to JC and Andy about the latest clinical results and modalities discussed at the 2024 Keystone symposium on Precision Genome Engineering.   4:07 Impacting patients6:44 In vivo editing in different liver diseases11:37 The FDA stance on programmable therapy19:41 Base-editors march into the clinic25:54 Multiplexing with base editors28:57 Reaching broader patient populations33:32 Investigator-initiated trials39:27 Prime and epigenetic editing44:34 Excitement around Bridge RNAs 47:15 Kiran’s mocktailBloody Mary 3 Ways4oz (120 ml) tomato juice1/2oz (15 ml) fresh lemon juice1/4oz (7 ml) Worcestershire sauce1/2 barspoon (3 ml) prepared horseradish, or to taste2 dashes Tabasco, or to tasteCelery stick, for garnishSalt and freshly ground pepperYour choice of pickled vegetables, skewered on a cocktail pick, for garnishDIRECTIONS: Add the tomato juice, lemon juice, Worcestershire, horseradish, and Tabasco to a shaker tin with ice and gently shake for 5 seconds.  Strain into a chilled double rocks glass over a large ice cube. Garnish with the celery stick, salt, pepper, and pickled vegetables and serve. For alcoholophiles, add 2oz (60 ml) vodka to the tomato juice, lemon, Worcestershire, horseradish and Tabasco. Enjoy!Refs:Gilmore et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med 385, 493-502 (2021) DOI: 10.1056/NEJMoa2107454Chiesa et al . Base-edited CAR7 T cells for relapsed T-cell acute lymphoblastic leukemia.  N Engl J Med 389, 899-910 (2023) DOI: 10.1056/NEJMoa2300709 Longhurst et al. CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema N Engl J Med 390, 432-441 (2024) DOI: 10.1056/NEJMoa2309149Durrant et al. Bridge RNAs direct modular and programmable recombination of target and donor DNA.  https://www.biorxiv.org/content/10.1101/2024.01.24.577089v1Keystone Meeting on Precision Genome EngineeringSomatic Cell Genome Editing ConsortiumThe Mixer music “Pour Me Another” courtesy of Smooth Moves!