[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-352677-105":59,"doc-detail-352677-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","dual-targeting-of-mutant-p53-and-snrpd2-via-engineered-exosomes-modulates-alternative-splicing-to-suppress-ovarian-cancer","Dual Targeting of Mutant p53 and SNRPD2 via Engineered Exosomes Modulates Alternative Splicing to Suppress Ovarian Cancer","","Mutation of the tumor suppressor gene TP53 promotes ovarian cancer progression and therapeutic resistance, yet whether mutant p53 controls alternative splicing and how to leverage this for treatment remains unclear. SNRPD2 is identified as a binding partner of mutant p53, is highly expressed and linked to poor prognosis, and functionally drives ovarian cancer cell growth and migration. Mechanistically, mutant p53 and SNRPD2 cooperate to assemble the Sm/SMN spliceosomal complex, shifting alternative splicing to reduce oncogenic transcripts and increase tumor suppressor counterparts. Engineered exosomes decorated with iRGD and loaded with siRNAs against mutant p53 and SNRPD2 suppress tumor cell growth and improve chemosensitivity in vivo. Overall, co-targeting these regulators via engineered exosomes provides a potential therapeutic strategy for ovarian cancer.",{"@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/dual-targeting-of-mutant-p53-and-snrpd2-via-engineered-exosomes-modulates-alternative-splicing-to-suppress-ovarian-cancer/352677/",{"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/dual-targeting-of-mutant-p53-and-snrpd2-via-engineered-exosomes-modulates-alternative-splicing-to-suppress-ovarian-cancer/352677.png","ImageObject",300,407,{"name":92,"@type":93},"WPS_1786070896","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does mutant p53 play in ovarian cancer alternative splicing?","Question",{"text":112,"@type":113},"The study investigates whether mutant p53 regulates alternative splicing and proposes that mutant p53 cooperates with SNRPD2 to modulate spliceosome activity and splicing outcomes relevant to tumor progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does SNRPD2 affect ovarian cancer cells?",{"text":117,"@type":113},"SNRPD2 is highly expressed in ovarian cancer and is associated with an unfavorable prognosis; overexpression promotes, while depletion inhibits, ovarian cancer cell growth and migration.",{"name":119,"@type":110,"acceptedAnswer":120},"How do engineered exosomes target mtp53 and SNRPD2 therapeutically?",{"text":121,"@type":113},"Engineered exosomes are decorated with iRGD and loaded with siRNAs targeting mtp53 and SNRPD2, which suppress ovarian cancer cell growth and enhance chemosensitivity in vivo.","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},352677,1790179362,{"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":14,"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},549768072016,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Advanced Science    \n[www.advancedscience.com](www.advancedscience.com)  \n RESEARCH ARTICLE   \nDual Targeting of Mutant p53 and SNRPD2 via Engineered Exosomes Modulates Alternative Splicing to Suppress Ovarian Cancer  \nWei Zhao1, 2, 3  Qian Hao4, 5  Yu Gan4, 5  Jing Tong4, 5  Xiaodan Chen1, 2, 3  Shuran Tan1, 2, 3  Ruiwen Ruan6, 7  Yingdan Huang4, 5  Mingming Cao4, 5  Jun Deng6, 7  Tao Han8  Getao Shi9  Bo Gao9  Yu Zhang1, 2, 3  Xiang Zhou4, 5, 10   \n1 Department of Gynecology, Xiangya Hospital, Central South University, Changsha, China  2 Gynecological Oncology Research and Engineering Center of Hunan Province, Changsha, China  3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China  4 Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China  5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China  6 Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China  7Jiangxi Key Laboratory For Individual Cancer Therapy, Nanchang, Jiangxi, China  8Xinxiang Key laboratory For Molecular Oncology, Institutes of Health Central Plains, Xinxiang Medical University, Xinxiang, China  9Umibio Co. Ltd., Shanghai, China  10 Key Laboratory of Breast  \nCancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China Correspondence: Bo Gao ([bogao@umibio.cn](bogao@umibio.cn))  Yu Zhang (xyzhangyu@csu.edu.cn)  Xiang Zhou (xiangzhou@fudan.edu.cn)  \nReceived: 16 July 2025  Revised: 12 December 2025  Accepted: 6 January 2026  \nKeywords: alternative splicing | engineered exosomes | p53 | SNRPD2 | targeted therapy  \nABSTRACT  \nMutation of the tumor suppressor gene TP53 promotes ovarian cancer progression and therapeutic resistance. Whether mutant p53 (mtp53) regulates alternative splicing and how this regulation can be exploited for cancer therapy remain unclear. Here, small nuclear ribonucleoprotein D2 polypeptide (SNRPD2) as a binding partner of mtp53 is identified. SNRPD2 is highly expressed in ovarian cancer and associated with an unfavorable prognosis. The overexpression of SNRPD2 promotes, whereas its depletion inhibits, the growth and migration of ovarian cancer cells. Mechanistically, mtp53 cooperates with SNRPD2 to facilitate the assembly of the Sm/SMN protein complex, an essential component of the spliceosome, modulating alternative splicing of premRNAs. Specifically, the co-depletion of mtp53 and SNRPD2 reduces the level of OTUD3 oncogenic transcripts while increasing its tumor suppressor counterparts through an exon-skipping event. Moreover, therapeutic engineered exosomes are developed with their surfaces decorated with iRGD and their interiors loaded with siRNAs targeting mtp53 and SNRPD2 . These exosomes effectively suppress the growth of ovarian cancer cells and enhance their sensitivity to chemotherapy in vivo. Collectively, this study uncovers that mtp53 and SNRPD2 cooperatively regulate alternative splicing to drive ovarian cancer progression, and co-targeting these two molecules via engineered exosomes represents a potential therapeutic strategy for ovarian cancer.  \n1  Introduction  \nOvarian cancer, characterized by frequent relapse and inherent chemotherapy resistance, ranks among the most lethal gynecological malignancies [1] . Despite the continuous development  \nof novel therapeutic strategies, clinical management remains severely challenged by the high relapse rate and chemotherapy resistance [2–4] . TP53 mutations represent a cornerstone molecular alteration in ovarian cancer (OC), particularly in high-grade serous ovarian carcinoma (HGSOC), with profound clinical and  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is pr","cbCaismMFhMWHJLi","https://ap.wps.com/l/cbCaismMFhMWHJLi","pdf",13018529,18,"English","# Abstract\n# Introduction\n## Ovarian cancer burden and TP53 mutations\n## Alternative splicing and cancer resistance\n## Mutant p53 and RNA splicing regulation\n## SNRPD2/SmD2 as a spliceosomal Sm protein component","[{\"question\":\"What role does mutant p53 play in ovarian cancer alternative splicing?\",\"answer\":\"The study investigates whether mutant p53 regulates alternative splicing and proposes that mutant p53 cooperates with SNRPD2 to modulate spliceosome activity and splicing outcomes relevant to tumor progression.\"},{\"question\":\"How does SNRPD2 affect ovarian cancer cells?\",\"answer\":\"SNRPD2 is highly expressed in ovarian cancer and is associated with an unfavorable prognosis; overexpression promotes, while depletion inhibits, ovarian cancer cell growth and migration.\"},{\"question\":\"How do engineered exosomes target mtp53 and SNRPD2 therapeutically?\",\"answer\":\"Engineered exosomes are decorated with iRGD and loaded with siRNAs targeting mtp53 and SNRPD2, which suppress ovarian cancer cell growth and enhance chemosensitivity in vivo.\"}]","Dual Targeting of Mutant p53 and SNRPD2 via Engineered Exosomes Modulates Alternative Splicing to Suppress Ovarian Cancer | PDF",1790100804,45]