[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332628-105":59,"doc-detail-332628-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","crispr-mediated-ablation-of-tp53-and-egfr-mutations-enhances-gefitinib-sensitivity-and-anti-tumor-efficacy-in-lung-cancer","CRISPR-mediated ablation of TP53 and EGFR mutations enhances gefitinib sensitivity and anti-tumor efficacy in lung cancer","","Multiple pathogenic SNPs worsen cancer prognosis and drive drug resistance, including in lung cancer where EGFR inhibitor resistance limits durable responses. Targeting EGFR and TP53 oncogenes carrying EGFR-T790M and TP53-R273H missense mutations, adenine base editor (ABE) and SNP-specific guide RNAs were co-delivered via adenovirus for precise, accurate correction in vitro and in vivo. Compared with gefitinib alone, SNP-targeted Ad/ABE co-treatment increased drug sensitivity and suppressed abnormal tumor growth more effectively, supporting ABE correction of dual oncogenic SNPs as an approach for drug-resistant cancer therapy.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/crispr-mediated-ablation-of-tp53-and-egfr-mutations-enhances-gefitinib-sensitivity-and-anti-tumor-efficacy-in-lung-cancer/332628/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/crispr-mediated-ablation-of-tp53-and-egfr-mutations-enhances-gefitinib-sensitivity-and-anti-tumor-efficacy-in-lung-cancer/332628.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What dual mutations were targeted in this study?","Question",{"text":112,"@type":113},"The study targeted mutated EGFR and TP53 oncogenes with EGFR-T790M and TP53-R273H missense mutations associated with gefitinib resistance.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the gene correction delivered?",{"text":117,"@type":113},"Adenine base editor (ABE) and EGFR- and TP53-SNP specific single-guide RNAs were co-delivered via adenovirus, enabling precise correction in vitro and in vivo.",{"name":119,"@type":110,"acceptedAnswer":120},"How did the combination treatment compare with gefitinib alone?",{"text":121,"@type":113},"Compared with gefitinib treatment alone, Ad/ABE co-treatment targeting SNPs in TP53 and EGFR increased gefitinib sensitivity and more efficiently suppressed abnormal tumor growth.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332628,1790099210,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","Original Article  \nCRISPR-mediated ablation of TP53 and EGFR mutations enhances gefitinib sensitivity and anti-tumor efficacy in lung cancer  \nA-Rum Yoon, 1,2,3 Soyeon Lee,4 Ju Hee Kim, 1 Yejin Park,4 Taeyoung Koo,4 and Chae-Ok Yun 1,2,3,5  \n1Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea; 2Institute of Nano Science and Technology (INST), Hanyang University, Seoul, Republic of Korea; 3Hanyang Institute of Bioscience and Biotechnology (HY-IBB), Hanyang University, Seoul, Republic of Korea; 4College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; 5GeneMedicine Co., Ltd., 222 Wangsimni-ro, Seongdong-gu, Seoul, Republic of Korea  \nMultiple pathogenic single-nucleotide polymorphisms (SNPs) have been identified as contributing factors in the aggravation of cancer prognosis and emergence of drug resistance in various cancers. Here, we targeted mutated EGFR and TP53 oncogenes harboring single-nucleotide missense mutations (EGFR-T790M and TP53-R273H) that are associated with gefitinib resistance. Co-delivery of adenine base editor (ABE) and EGFR- and TP53-SNP specific single-guide RNA via adenovirus (Ad) resulted in precise correction of the oncogenic mutations with high accuracy and efficiency in vitro and in vivo. Importantly, compared with a control group treated only with gefitinib, an EGFR inhibitor, co-treatment with Ad/ABE targeting SNPs in TP53 and EGFR in combination with gefitinib increased drug sensitivity and suppressed abnormal tumor growth more efficiently. Taken together, these results indicate that ABE-mediated correction of dual oncogenic SNPs can bean effective strategy for the treatment of drug-resistant cancers.  \nINTRODUCTION  \nNon-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases.1 Despite targeted therapeutics, such as tyrosine kinase inhibitors (TKIs), which have revolutionized the treatment of NSCLC, medical unmet needs persist due to the emergence of drug resistance.2,3 For instance, the acquired resistance to gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) and a first-line therapy for lung cancer treatment, has faced significant challenges, predominantly due to the development of secondary genetic mutations. Following repeated drug exposure, recurrent missense mutation within the tyrosine kinase domain of the EGFR gene is commonly found at exon 20 (T790M), thereby compromising its therapeutic efficacy in treating NSCLC.3,4 In addition, concurrent alterations further potentiate resistance to the EGFR inhibitors. Interestingly, patients harboring double mutations in the EGFR and TP53 tumor suppressor genes demonstrated a marked lack of therapeutic response to subsequent EGFR-targeted therapy.5,6 Specifically, TP53-R273H mutant has been shown to accelerate acquired resistance to EGFR-TKIs in NSCLC with EGFR mutation through the induction of epithelial-to-mesenchymal transition (EMT) .7 This observation underscores the complex interplay of genetic factors in  \ndictating the efficacy of targeted therapies in oncology. Consequently, targeted gene editing directed both at the EGFR-T790M and TP53-R273H mutations emerges as a promising strategy to counteract drug resistance and augment the therapeutic effectiveness of EGFRTKIs in the treatment of NSCLC.  \nThe CRISPR-Cas system, an adaptive immune system in bacteria and archaea for viral defense, has been ingeniously repurposed for precise genome editing, offering a therapeutic tool for the treatment of abroad spectrum of genetic or non-genetic disorders.8–12 Specifically, the Cas9 protein derived from Streptococcus pyogenes (SpCas9), when employed with a single-guide RNA (sgRNA), induces site-specific DNA cleavage upstream of a protospacer adjacent motif (PAM) . This results in insertions and deletions (indels) at the cleavage site through the non-homologous end joining (NHEJ) pathway, leading to either in-frame mutations or knockout (KO) of the targeted g","cbCaid9kiB5tZgDv","https://ap.wps.com/l/cbCaid9kiB5tZgDv","pdf",3727918,11,"English","# Introduction\n## Targeted therapy and resistance in NSCLC\n## CRISPR-Cas genome editing and limitations\n## Rationale for mutation-specific ABE editing","[{\"question\":\"What dual mutations were targeted in this study?\",\"answer\":\"The study targeted mutated EGFR and TP53 oncogenes with EGFR-T790M and TP53-R273H missense mutations associated with gefitinib resistance.\"},{\"question\":\"How was the gene correction delivered?\",\"answer\":\"Adenine base editor (ABE) and EGFR- and TP53-SNP specific single-guide RNAs were co-delivered via adenovirus, enabling precise correction in vitro and in vivo.\"},{\"question\":\"How did the combination treatment compare with gefitinib alone?\",\"answer\":\"Compared with gefitinib treatment alone, Ad/ABE co-treatment targeting SNPs in TP53 and EGFR increased gefitinib sensitivity and more efficiently suppressed abnormal tumor growth.\"}]","CRISPR-mediated ablation of TP53 and EGFR mutations enhances gefitinib sensitivity and anti-tumor efficacy in lung cancer | PDF",1789998953,28]