دورية أكاديمية
Nonviral CRISPR/Cas9 mutagenesis for streamlined generation of mouse lung cancer models.
| العنوان: | Nonviral CRISPR/Cas9 mutagenesis for streamlined generation of mouse lung cancer models. |
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| المؤلفون: | Lara-Sáez I; Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield, Dublin D04 V1W8, Ireland., Mencía Á; Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid 28040, Spain.; CB06/07/0019 Unit, Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid 28029, Spain.; Regenerative Medicine and Tissue Bioengineering Group, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid 28040, Spain., Recuero E; Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid 28040, Spain.; Cellular and Molecular Genitourinary Oncology Group, Institute of Biomedical Research Hospital '12 de Octubre', Madrid 28041, Spain., Li Y; Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield, Dublin D04 V1W8, Ireland., García M; CB06/07/0019 Unit, Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid 28029, Spain.; Regenerative Medicine and Tissue Bioengineering Group, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid 28040, Spain.; Department of Biomedical Engineering, Polytechnic School, Carlos III University, Leganés, Madrid 28911, Spain., Oteo M; Biomedical Applications and Pharmacokinetics Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid 28040, Spain., Gallego MI; Unidad de Histología, Unidades Centrales Científico Tecnológicas, Instituto de Salud Carlos III, Madrid 28220, Spain., Enguita AB; Pathology Department, University Hospital '12 de Octubre', Madrid 28041, Spain., de Prado-Verdún D; Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid 28040, Spain.; CB06/07/0019 Unit, Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid 28029, Spain.; Regenerative Medicine and Tissue Bioengineering Group, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid 28040, Spain., A S; Research and Clinical Translation Center of Gene Medicine and Tissue Engineering, School of Public Health, Anhui University of Science and Technology, Huainan 232001, China., Wang W; Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield, Dublin D04 V1W8, Ireland., García-Escudero R; Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid 28040, Spain.; Cellular and Molecular Genitourinary Oncology Group, Institute of Biomedical Research Hospital '12 de Octubre', Madrid 28041, Spain.; Tumor Progression Mechanisms Program, Centro de Investigación Biomédica en Red de Cáncer, Madrid 28029, Spain., Murillas R; Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid 28040, Spain.; CB06/07/0019 Unit, Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid 28029, Spain.; Regenerative Medicine and Tissue Bioengineering Group, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid 28040, Spain., Santos M; Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid 28040, Spain.; Cellular and Molecular Genitourinary Oncology Group, Institute of Biomedical Research Hospital '12 de Octubre', Madrid 28041, Spain.; Tumor Progression Mechanisms Program, Centro de Investigación Biomédica en Red de Cáncer, Madrid 28029, Spain. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 09; Vol. 121 (28), pp. e2322917121. Date of Electronic Publication: 2024 Jul 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Lung Neoplasms*/genetics , Lung Neoplasms*/pathology , CRISPR-Cas Systems* , PTEN Phosphohydrolase*/genetics , Tumor Suppressor Protein p53*/genetics , Small Cell Lung Carcinoma*/genetics , Small Cell Lung Carcinoma*/pathology , Mutagenesis*, Animals ; Mice ; Humans ; Disease Models, Animal ; Retinoblastoma-Like Protein p107/genetics ; Retinoblastoma-Like Protein p107/metabolism ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Gene Editing/methods |
| مستخلص: | Functional analysis in mouse models is necessary to establish the involvement of a set of genetic variations in tumor development. A modeling platform to facilitate and cost-effectively analyze the role of multiple genes in carcinogenesis would be valuable. Here, we present an innovative strategy for lung mutagenesis using CRISPR/Cas9 ribonucleoproteins delivered via cationic polymers. This approach allows the simultaneous inactivation of multiple genes. We validate the effectiveness of this system by targeting a group of tumor suppressor genes, specifically Rb1 , Rbl1 , Pten , and Trp53 , which were chosen for their potential to cause lung tumors, namely small cell lung carcinoma (SCLC). Tumors with histologic and transcriptomic features of human SCLC emerged after intratracheal administration of CRISPR/polymer nanoparticles. These tumors carried loss-of-function mutations in all four tumor suppressor genes at the targeted positions. These findings were reproduced in two different pure genetic backgrounds. We provide a proof of principle for simplified modeling of lung tumorigenesis to facilitate functional testing of potential cancer-related genes. Competing Interests: Competing interests statement:W.W. is the Founder of Branca Bunús, a University College Dublin (UCD) start-up company that manufactures branched polymers for gene delivery and in which UCD is involved in collaborative research projects. |
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| معلومات مُعتمدة: | IDEAS211079SANT Fundación Científica Asociación Española Contra el Cáncer (AECC); CB16/12/00228/CIBERONC MEC | Instituto de Salud Carlos III (ISCIII); PI21/00764 MEC | Instituto de Salud Carlos III (ISCIII); PI21/00171 MEC | Instituto de Salud Carlos III (ISCIII); PI15/00993 MEC | Instituto de Salud Carlos III (ISCIII); 18/FIP/3576 Science Foundation Ireland (SFI); 19/FFP/6522 Science Foundation Ireland (SFI); CSC202008300033) China Scholarship Council (CSC); Garcia-Diez 1 Debra International (DEBRA) |
| فهرسة مساهمة: | Keywords: CRISPR/Cas9 ribonucleoprotein; SCLC; in vivo gene editing; lung cancer models |
| المشرفين على المادة: | EC 3.1.3.67 (PTEN Phosphohydrolase) 0 (Tumor Suppressor Protein p53) EC 3.1.3.67 (Pten protein, mouse) 0 (Rbl1 protein, mouse) 0 (Trp53 protein, mouse) 0 (Retinoblastoma-Like Protein p107) 0 (Retinoblastoma Protein) |
| تواريخ الأحداث: | Date Created: 20240703 Date Completed: 20240703 Latest Revision: 20240719 |
| رمز التحديث: | 20240719 |
| مُعرف محوري في PubMed: | PMC11252735 |
| DOI: | 10.1073/pnas.2322917121 |
| PMID: | 38959035 |
| قاعدة البيانات: | MEDLINE |
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