Gene Therapy最新文献

{"title":"First pilot study of intravenous rAAV-PAX6 gene therapy increases retinal-ganglion-cell-layer thickness and Notch1 transcription in a mouse model of aniridia.","authors":"Diana Djaksigulova, Sif G Kaad, Andrea J Korecki, Siu Ling Lam, Tess C Lengyell, Elizabeth M Simpson","doi":"10.1038/s41434-026-00605-5","DOIUrl":"https://doi.org/10.1038/s41434-026-00605-5","url":null,"abstract":"<p><p>Aniridia is a rare congenital vision-loss disorder that is caused primarily by heterozygous loss-of-function variants in the PAX6 gene. There is currently no curative treatment. Gene therapy has emerged as a powerful strategy for treating inherited retinal diseases. Here, we aim to establish a systemic PAX6 gene-augmentation therapy capable of addressing retinal pathologic phenotypes in a preclinical Sey mouse model of aniridia. We evaluated the intravenous delivery of FLAG-tagged PAX6 packaged in the AAV-PHP.eB capsid. Treatment was administered on postnatal day 21 to mimic the average age at diagnosis and the likely early therapeutic window in humans. The transcript levels of the virally-delivered PAX6 were 7.1% at 1 month, and 8.9% at 5 months, of Wt endogenous levels. These transcripts produced PAX6 protein in the ganglion (GCL) and inner nuclear cell layers. Importantly, in this pilot study, a significant increase in GCL thickness at 5 months post-injection was also observed. Furthermore, this structural change in the Sey retina was preceded by a significant increase in Notch1 transcription at 1-month post-injection. Thus, we demonstrated the first successful viral-mediated augmentation of PAX6 in the retina in a preclinical mouse model of aniridia, resulting in a phenotypic change at the structural and molecular levels.</p>","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo rescue of dopaminergic neurons in Parkinson’s disease models after Parkin gene therapy","authors":"Takeshi Hioki,&nbsp;Masaaki Nishimura,&nbsp;Xiuxia Sun,&nbsp;Sarah Melissa Jacobo,&nbsp;Miyu Nakayama,&nbsp;Mitsuhiro Nishihara,&nbsp;Kimio Tohyama,&nbsp;Po-Ting Liu,&nbsp;Takuro Okai,&nbsp;Maiko Tanaka,&nbsp;Gabriele Proetzel","doi":"10.1038/s41434-026-00599-0","DOIUrl":"10.1038/s41434-026-00599-0","url":null,"abstract":"Young-onset Parkinson’s disease (PD), the most common autosomal recessive familial PD, is caused by gene mutations in Parkin (PRKN). These mutations result in Parkin protein loss and reduced enzymatic activity, leading to severe degeneration of dopamine-producing neurons in the substantia nigra pars compacta (SNpc). Adeno-associated virus (AAV) gene therapy can directly address the cause of PRKN-PD by expressing Parkin protein at levels comparable to those observed in healthy humans. AAV9 vectors with different promoters were engineered to deliver PRKN cDNA with efficient human Parkin (hParkin) expression in dopaminergic (DA) neurons as shown in PRKN-null human induced pluripotent stem cell (iPSC) derived DA neurons. Further, we show that AAV9-PRKN treatment can protect nigral DA neurons in two mouse PD models, the 6-hydroxydopamine (6-OHDA)-lesion and the α-synuclein (α-Syn) pre-formed fibrils (PFFs)-lesion model. In summary, AAV9-PRKN gene therapy demonstrates neuroprotective properties and may represent a promising approach for PRKN-PD, with potential broader applications in idiopathic PD and other neurodegenerative diseases.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"33 4","pages":"448-461"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41434-026-00599-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virus-mediated gene transfer of soluble amyloid precursor protein-alpha via systemic injection in a mouse model of Alzheimer’s disease","authors":"Yuanyuan He,&nbsp;Bruce G. Mockett,&nbsp;Lucia Schoderboeck,&nbsp;Kirstin O. McDonald,&nbsp;Barbara J. Logan,&nbsp;Shruthi Sateesh,&nbsp;Owen D. Jones,&nbsp;Stephanie M. Hughes,&nbsp;Wickliffe C. Abraham","doi":"10.1038/s41434-026-00602-8","DOIUrl":"10.1038/s41434-026-00602-8","url":null,"abstract":"Alzheimer’s disease (AD) is the most common neurodegenerative disorder, yet effective preventive or therapeutic strategies remain limited. A hallmark of AD pathology is the accumulation of insoluble amyloid-β (Aβ) aggregates, which are targeted by recent antibody-based therapies. Conversely, soluble amyloid precursor protein-alpha (sAPPα), a non-amyloidogenic cleavage product of APP, possesses neuroprotective, neurotrophic, and synaptogenic properties, and the ability to enhance memory. This study evaluated the therapeutic efficacy of adeno-associated virus variant PHP.eB (AAV-PHP.eB) encoding human sAPPα in the APPswe/PS1dE9 transgenic mouse model of AD. Six-month-old female wild-type and transgenic mice received a single intravenous injection via the tail vein. Three months post-injection, brain tissue was harvested for electrophysiological and histological analyses. The treatment significantly increased cortical sAPPα levels and fully restored hippocampal long-term potentiation (LTP) in transgenic mice. Post-mortem analyses revealed a substantial reduction in amyloid plaque burden in both the hippocampus and cortex, with minimal plaque progression from the time of injection. However, no significant changes were observed in astrocytic (GFAP) or microglial (Iba-1) coverage, nor in soluble and insoluble Aβ1-40 or Aβ1-42 levels. These findings suggest that systemic AAV-PHP.eB-mediated sAPPα delivery can ameliorate synaptic dysfunction and aggregated amyloid pathology in AD, highlighting its potential as a therapeutic strategy.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"33 4","pages":"474-485"},"PeriodicalIF":5.9,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41434-026-00602-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-guided left heart injection: a safer and more efficient strategy for mouse thoracic aortic gene delivery","authors":"Yanmiao Yang,&nbsp;Kunyao Xu,&nbsp;Ya Yuan,&nbsp;Bo Huang,&nbsp;Shan Wei,&nbsp;Yi Zhao,&nbsp;Yang Song,&nbsp;Daxing Liu,&nbsp;Jianguo Liu,&nbsp;Dengshen Zhang","doi":"10.1038/s41434-026-00603-7","DOIUrl":"10.1038/s41434-026-00603-7","url":null,"abstract":"Thoracic aortic disease poses a significant threat due to its high mortality rates and genetic. underpinnings. While gene therapy holds promise for cures, the challenge lies in achieving. effective and safe gene delivery to the thoracic aorta. Tail vein injection (TI), is hindered by. off-target effects and hepatotoxicity, and traditional blinded percutaneous left heart injection. (TLI) carries a heightened risk of bleeding and mortality. To address these limitations. ultrasound-guided techniques present a viable solution. Adeno-associated virus (AAV) vectors. were delivered into the thoracic aorta of mice through TI, TLI, and ultrasound-guided. percutaneous left heart injection(ULI). While all three injection methods can achieve gene transduction in the thoracic aorta, the ULI approach provides the optimal balance between. high transduction efficiency and safety. The ULI method represents an efficient and safe. strategy for targeted gene delivery to the mouse thoracic aorta, providing a powerful tool for preclinical aortic gene therapy research that warrants broader application.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"33 2","pages":"176-187"},"PeriodicalIF":4.5,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of gene therapy for sickle cell disease in Uganda: tailoring high-income evidence to Uganda’s context","authors":"J. Felipe Montano-Campos,&nbsp;Jennifer E. Adair,&nbsp;Anirban Basu,&nbsp;Rachel Bakyayita Kyeyune,&nbsp;Lois Bayigga,&nbsp;Cissy Kityo-Mutuluuza,&nbsp;Ryan Hansen","doi":"10.1038/s41434-026-00598-1","DOIUrl":"10.1038/s41434-026-00598-1","url":null,"abstract":"Blood stem cell gene therapy to treat hemoglobinopathies is beginning to transform health for small numbers of patients in the U.S. and Europe, where these conditions qualify as rare diseases. Yet hemoglobinopathies are common globally, disproportionately affecting low- and middle-income countries (LMICs), creating an ethical imperative to ensure access where disease burden is greatest. Gene therapy could have blockbuster drug potential if distributable to these regions, but cost is a major barrier. Cost-effectiveness analysis (CEA) models are seldom adapted to low-income settings, where limited data and resources constrain efforts to contextualize high-income evidence. Here, we present a novel framework to evaluate high-income country authorized gene therapies in LMIC contexts. Uganda, where sickle cell disease (SCD) imposes a major burden and no curative therapies are available, is the test case. We evaluate cost-effectiveness of gene therapy for adolescents and adults with SCD in Uganda, adapting U.S. evidence to local economic conditions. Using a three-state Markov model to estimate lifetime costs of standard-of-care in Uganda, two U.S.-based CEA models were adapted using scaling factors and applied to two authorized gene therapies for SCD, Lyfgenia™ (lovo-cel) and Casgevy® (exa-cel), assuming biologically consistent efficacy across populations. Incremental cost-effectiveness ratios (ICERs) were calculated from healthcare and societal perspectives, with internationally accepted gross domestic product-based thresholds. This study demonstrates that Casgevy could be cost-effective in Uganda at a scaled cost when societal benefits are considered. This framework enables CEAs for emerging therapies where local clinical trial data are limited, supporting local decision-makers, global funders, and manufacturers in advancing equitable access to transformative therapies in LMICs.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"33 2","pages":"109-117"},"PeriodicalIF":4.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41434-026-00598-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147304944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization and scale up strategies for reproducible AAV enrichment step on CIMmultus® QA HR line","authors":"Rok Žigon,&nbsp;Sara Drmota Prebil,&nbsp;Tomaž Švigelj,&nbsp;Kaja Kozjak,&nbsp;Timotej Žvanut,&nbsp;Maja Leskovec,&nbsp;Aleš Štrancar","doi":"10.1038/s41434-026-00594-5","DOIUrl":"10.1038/s41434-026-00594-5","url":null,"abstract":"The advancement of adeno-associated virus (AAV) gene therapy applications faces significant challenges, particularly in the separation of empty (E), full (F), and intermediate capsids during manufacturing, as well as scaling up downstream processing. This study demonstrates the effectiveness of monolithic chromatography in maintaining high flow rates without sacrificing resolution across scales, making it ideal for large-scale applications. The CIMmultus® HR columns ensure high reproducibility at various purification scales, achieving ± 3% isoconductivity elution of empty AAV2/8 capsids. In combination with the improved method, it enriches full AAV capsids to 88% ± 9% with genome recovery of 77% ± 3% within this study. The screening of polishing columns exhibited highest enrichment and recovery of full capsids with an improved method developed on QA HR preparative column. High-throughput screening (HTS) on CIM® QA HR Monolithic Well Plate and subsequent single-column experiments confirmed these findings, facilitating predictions for implementing step elution approaches. The high reproducibility of the columns enabled the development of step elution methods in both bind-elute and flow through modes, with both approaches yielding comparable recovery and purity of full AAV capsids. Ultimately, the optimized AAV polishing method was successfully scaled up from 1 to 8000 mL monolith using step elution approach.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"33 3","pages":"296-309"},"PeriodicalIF":4.5,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41434-026-00594-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drinkable gene therapy foam for the treatment of constrictive esophageal carcinoma","authors":"Sirkka B. Stephan,&nbsp;Carrie L. Cummings,&nbsp;Katelyn Fitzgerald,&nbsp;Matthias T. Stephan","doi":"10.1038/s41434-026-00592-7","DOIUrl":"10.1038/s41434-026-00592-7","url":null,"abstract":"Patients diagnosed with esophageal cancer (EC) currently rely on treatments given at specialist care centers (surgery, chemotherapy, radiation), which despite their low cure rates are extremely life-disruptive, cause severe pain, and have strong side effects. In particular, dysphagia is one of the most distressing and debilitating symptoms in patients with cancer-related esophageal obstruction. There is clearly an urgent need for new effective and accessible therapies for EC patients that allow patients to continue normal activity as much as possible. Here, we describe a drinkable methylcellulose/xanthan gum-based gene therapy foam that coats the esophagus and accumulates an apoptosis-inducing gene therapy drug (mRNA lipid nanoparticles encoding Pseudomonas exotoxin A) at the tumorous esophageal stricture. In an in vitro EC tissue model, we show that gene therapy foam induces 110-fold higher tumor regression compared to suspension treatment. We also establish that gene therapy foam given prior to radiotherapy strongly enhances anti-tumor effects. Once implemented in the clinic, this treatment, which can be administered orally by a local family doctor or at home by the patient or caregiver, could maximize the time EC patients can live normal lives outside of the hospital and allow them to maintain their ability to swallow and eat.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"33 2","pages":"118-126"},"PeriodicalIF":4.5,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41434-026-00592-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AAV-based gene therapies for neovascular AMD","authors":"Tae Hee Kim,&nbsp;Chan You Kwon,&nbsp;Jae Yoon Song,&nbsp;Hee Chan Yoo","doi":"10.1038/s41434-026-00595-4","DOIUrl":"10.1038/s41434-026-00595-4","url":null,"abstract":"Neovascular age-related macular degeneration (nAMD) is a major cause of irreversible vision loss in the elderly, driven by choroidal neovascularization and dysregulated vascular endothelial growth factor (VEGF) signaling. While anti-VEGF injections have transformed management, their frequent administration imposes a substantial burden on patients and limits adherence. Adeno-associated virus (AAV)-based gene therapy offers sustained intraocular delivery of anti-angiogenic agents with a single treatment, potentially overcoming these limitations. This review summarizes the rationale for AAV use in ocular gene therapy, compares major delivery routes, and highlights leading clinical candidates, including RGX-314, ADVM-022, 4D-150, and NG101. Advances in vector engineering, promoter optimization, and immune modulation are discussed alongside key challenges such as preexisting immunity and inflammation. Future directions include next-generation capsids, combination regimens, and precision patient selection. Collectively, these developments position AAV-based gene therapy as a promising strategy to redefine the therapeutic landscape of nAMD.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"33 4","pages":"383-397"},"PeriodicalIF":5.9,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41434-026-00595-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive forced degradation study revealing diverse chemical and physical degradation pathways of AAV8","authors":"Kuan-Yu Lai,&nbsp;Song Nie,&nbsp;Yu-Chieh Ariel Chen,&nbsp;Timothy N. Tiambeng,&nbsp;Shuli Tang,&nbsp;Yu Huang,&nbsp;Yuetian Yan,&nbsp;Shashwat Mishra,&nbsp;Humam Al-Rubaye,&nbsp;Aynur Hermann,&nbsp;Nina Liu,&nbsp;Michael Rosconi,&nbsp;Ning Li,&nbsp;Mohammed Shameem,&nbsp;Shunhai Wang,&nbsp;Li Zhi,&nbsp;Dingjiang Liu","doi":"10.1038/s41434-026-00593-6","DOIUrl":"10.1038/s41434-026-00593-6","url":null,"abstract":"While recombinant adeno-associated virus (AAV) holds significant promise for effective and durable gene delivery for gene therapy, a thorough understanding of the critical quality attributes (CQAs) along with the degradation pathways of AAV under the various stresses that may occur during manufacturing, storage, and handling remains limited. To address this gap, we performed a comprehensive forced degradation study to elucidate the degradation pathways of AAV8 under a series of stress conditions, such as oxidation, extreme pH, high temperature, freeze-thaw, and agitation. Our results show that, under these stress conditions, distinct post-translational modifications (PTM), including methionine oxidation, asparagine deamidation, and aspartic acid isomerization, along with multiple physical degradation pathways, including capsid aggregation, viral protein fragmentation, and genome DNA leakage, could occur. Alterations in AAV8 biological activity were frequently attributed to the combination effect from chemical and physical degradation mechanisms. The results from this study provide a valuable insight into the establishment of stability-indicating methods and the identification of CQAs for AAV. It will also support the development of robust manufacturing process as well as stable and efficacious AAV gene therapy drug products.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"33 3","pages":"284-295"},"PeriodicalIF":4.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41434-026-00593-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baboon endogenous retrovirus (ERV) envelope pseudotyped lentiviral vectors outperform human ERV lentivectors for transduction of T, B, NK and HSPCs","authors":"Séverine Périan,&nbsp;Eva Castellano,&nbsp;Caroline Costa,&nbsp;Chiara Martinello,&nbsp;Anne Galy,&nbsp;Gisèle Froment,&nbsp;Rimas Orentas,&nbsp;Antonio Valeri,&nbsp;Els Verhoeyen","doi":"10.1038/s41434-025-00587-w","DOIUrl":"10.1038/s41434-025-00587-w","url":null,"abstract":"Previously, we confirmed that BaEV-LVs outperformed VSV-G-LVs for gene delivery or correction of human T cells, B cells, NK cells and HSPCs correlating with high expression of its receptors, ASCT-1 and ASCT-2 on these cells. Since HERV-W gp uses the same entry receptors, we compared transduction efficiencies for BaEV-LVs and HERV-W-LVs in hematopoietic cells. HERV-W LV transduction was efficient but inferior to BaEV-LV in TCR-stimulated T cells (40% versus 80%) and this low efficiency was even more pronounced in IL-7/IL-15 pre-stimulated T cells. BaEV-LVs were significantly superior over HERV-W-LVs for the transduction of B cells and NK cells. High HERV-W-LV mediated transduction levels were achieved for pre-stimulated hCD34+ cells, which remained though lower than for the BaEV-LVs. Additionally, BaEV-LVs reached over 80% of transduction in severe combined immunodeficiency (SCID) repopulating cells (SRC) in 6/6 engrafted NBSGW mice. HERV-W-LVs reached this transduction level in 1/5 mice, while 3/5 engrafted NBSGW mice reached significantly lower transduction levels (20–50%). For both vectors the transduction levels were equivalent in the lymphoid and myeloid lineages in all hematopoietic tissues, suggesting transduction of immature HSPCs. Summarizing, BaEV-LVs outperformed HERV-W-LVs for transduction of important gene therapy target cells such as NK, B, T cells and CD34+ HSPCs.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":"33 2","pages":"144-155"},"PeriodicalIF":4.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41434-025-00587-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}