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In vivo editing of lung stem cells for durable gene correction in mice.
Sun, Yehui; Chatterjee, Sumanta; Lian, Xizhen; Traylor, Zachary; Sattiraju, Sandhya R; Xiao, Yufen; Dilliard, Sean A; Sung, Yun-Chieh; Kim, Minjeong; Lee, Sang M; Moore, Stephen; Wang, Xu; Zhang, Di; Wu, Shiying; Basak, Pratima; Wang, Jialu; Liu, Jing; Mann, Rachel J; LePage, David F; Jiang, Weihong; Abid, Shadaan; Hennig, Mirko; Martinez, Anna; Wustman, Brandon A; Lockhart, David J; Jain, Raksha; Conlon, Ronald A; Drumm, Mitchell L; Hodges, Craig A; Siegwart, Daniel J.
  • Sun Y; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Chatterjee S; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Lian X; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Traylor Z; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • Sattiraju SR; ReCode Therapeutics, Menlo Park, CA 94025, USA.
  • Xiao Y; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Dilliard SA; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Sung YC; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Kim M; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Lee SM; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Moore S; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Wang X; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Zhang D; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Wu S; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Basak P; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Wang J; ReCode Therapeutics, Menlo Park, CA 94025, USA.
  • Liu J; ReCode Therapeutics, Menlo Park, CA 94025, USA.
  • Mann RJ; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • LePage DF; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • Jiang W; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • Abid S; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Hennig M; ReCode Therapeutics, Menlo Park, CA 94025, USA.
  • Martinez A; ReCode Therapeutics, Menlo Park, CA 94025, USA.
  • Wustman BA; ReCode Therapeutics, Menlo Park, CA 94025, USA.
  • Lockhart DJ; ReCode Therapeutics, Menlo Park, CA 94025, USA.
  • Jain R; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Conlon RA; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • Drumm ML; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • Hodges CA; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • Siegwart DJ; Department of Biomedical Engineering, Department of Biochemistry, Simmons Comprehensive Cancer Center, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science ; 384(6701): 1196-1202, 2024 Jun 14.
Article en En | MEDLINE | ID: mdl-38870301
ABSTRACT
In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Madre / Regulador de Conductancia de Transmembrana de Fibrosis Quística / Fibrosis Quística / Nanopartículas / Edición Génica / Liposomas / Pulmón Límite: Animals / Humans Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Madre / Regulador de Conductancia de Transmembrana de Fibrosis Quística / Fibrosis Quística / Nanopartículas / Edición Génica / Liposomas / Pulmón Límite: Animals / Humans Idioma: En Año: 2024 Tipo del documento: Article