Nucleic acid therapeutics最新文献_第4页

RNA Interference Effectors Selectively Silence the Pathogenic Variant GNAO1 c.607 G > A In Vitro. RNA 干扰效应器可选择性地抑制体外致病变体 GNAO1 c.607 G > A。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-04-01 Epub Date: 2024-01-12 DOI: 10.1089/nat.2023.0043

Natalia V Klementieva, Evgenii A Lunev, Anna A Shmidt, Elizaveta M Loseva, Irina M Savchenko, Ekaterina A Svetlova, Ivan I Galkin, Anna V Polikarpova, Evgeny V Usachev, Svetlana G Vassilieva, Valeria I Marina, Marina A Dzhenkova, Anna D Romanova, Anton V Agutin, Anna A Timakova, Denis A Reshetov, Tatiana V Egorova, Maryana V Bardina

{"title":"RNA Interference Effectors Selectively Silence the Pathogenic Variant GNAO1 c.607 G > A In Vitro.","authors":"Natalia V Klementieva, Evgenii A Lunev, Anna A Shmidt, Elizaveta M Loseva, Irina M Savchenko, Ekaterina A Svetlova, Ivan I Galkin, Anna V Polikarpova, Evgeny V Usachev, Svetlana G Vassilieva, Valeria I Marina, Marina A Dzhenkova, Anna D Romanova, Anton V Agutin, Anna A Timakova, Denis A Reshetov, Tatiana V Egorova, Maryana V Bardina","doi":"10.1089/nat.2023.0043","DOIUrl":"10.1089/nat.2023.0043","url":null,"abstract":"RNA interference (RNAi)-based therapeutics hold the potential for dominant genetic disorders, enabling sequence-specific inhibition of pathogenic gene products. We aimed to direct RNAi for the selective suppression of the heterozygous GNAO1 c.607 G > A variant causing GNAO1 encephalopathy. By screening short interfering RNA (siRNA), we showed that GNAO1 c.607G>A is a druggable target for RNAi. The si1488 candidate achieved at least twofold allelic discrimination and downregulated mutant protein to 35%. We created vectorized RNAi by incorporating the si1488 sequence into the short hairpin RNA (shRNA) in the adeno-associated virus (AAV) vector. The shRNA stem and loop were modified to improve the transcription, processing, and guide strand selection. All tested shRNA constructs demonstrated selectivity toward mutant GNAO1, while tweaking hairpin structure only marginally affected the silencing efficiency. The selectivity of shRNA-mediated silencing was confirmed in the context of AAV vector transduction. To conclude, RNAi effectors ranging from siRNA to AAV-RNAi achieve suppression of the pathogenic GNAO1 c.607G>A and discriminate alleles by the single-nucleotide substitution. For gene therapy development, it is crucial to demonstrate the benefit of these RNAi effectors in patient-specific neurons and animal models of the GNAO1 encephalopathy.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"90-99"},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

"Goldilocks Modifications" for mRNA Therapeutics Won the Nobel Prize. 用于 mRNA 治疗的 "金发修饰 "荣获诺贝尔奖。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-02-01 Epub Date: 2024-01-30 DOI: 10.1089/nat.2023.0062

Li Li

引用次数: 0

Report of the European Medicines Agency Conference on RNA-Based Medicines. 欧洲药品管理局关于基于 RNA 的药物会议的报告。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-02-01 Epub Date: 2024-01-04 DOI: 10.1089/nat.2023.0021

Falk Ehmann, Andreas Kuhn, Anna Maria Gerdina Pasmooij, Anthony Humphreys, Arjon Van Hengel, Brian Dooley, Brigitte Anliker, Camilla Svensson, Daniel Capaldi, David Henshall, Emer Cooke, Haiyan Zhou, Hilde Bastaerts, Jeske Smink, Joop Van Gerven, Leonor Enes, Lubomir Nechev, Marcel Hoefnagel, Mariëtte Driessens, Michael Wenger, Oriane Blanquie, Pawel Widomski, Ralf Herold, René Thürmer, Sol Ruiz, Steffen Thirstrup, Susan Goody, Tal Zaks, Valentina Cordò, Annemieke M Aartsma-Rus

{"title":"Report of the European Medicines Agency Conference on RNA-Based Medicines.","authors":"Falk Ehmann, Andreas Kuhn, Anna Maria Gerdina Pasmooij, Anthony Humphreys, Arjon Van Hengel, Brian Dooley, Brigitte Anliker, Camilla Svensson, Daniel Capaldi, David Henshall, Emer Cooke, Haiyan Zhou, Hilde Bastaerts, Jeske Smink, Joop Van Gerven, Leonor Enes, Lubomir Nechev, Marcel Hoefnagel, Mariëtte Driessens, Michael Wenger, Oriane Blanquie, Pawel Widomski, Ralf Herold, René Thürmer, Sol Ruiz, Steffen Thirstrup, Susan Goody, Tal Zaks, Valentina Cordò, Annemieke M Aartsma-Rus","doi":"10.1089/nat.2023.0021","DOIUrl":"10.1089/nat.2023.0021","url":null,"abstract":"RNA-based medicines have potential to treat a large variety of diseases, and research in the field is very dynamic. Proactively, The European Medicines Agency (EMA) organized a virtual conference on February 2, 2023 to promote the development of RNA-based medicines. The initiative addresses the goal of the EMA Regulatory Science Strategy to 2025 to \"catalyse the integration of science and technology in medicines development.\" The conference focused on RNA technologies (excluding RNA vaccines) and involved different stakeholders, including representatives from academia, industry, regulatory authorities, and patient organizations. The conference comprised presentations and discussion sessions conducted by panels of subject matter experts. In this meeting report, we summarize the presentations and recap the main themes of the panel discussions.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"4-11"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety and Tolerability of GalNAc₃-Conjugated Antisense Drugs Compared to the Same-Sequence 2'-O-Methoxyethyl-Modified Antisense Drugs: Results from an Integrated Assessment of Phase 1 Clinical Trial Data. GalNAc3共轭反义药物与同序列2'-O-甲氧基乙基修饰反义药物相比的安全性和耐受性：1期临床试验数据的综合评估结果。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-02-01 Epub Date: 2024-01-16 DOI: 10.1089/nat.2023.0026

Brenda F Baker, Shuting Xia, Wesley Partridge, Jeffery A Engelhardt, Sotirios Tsimikas, Stanley T Crooke, Sanjay Bhanot, Richard S Geary

{"title":"Safety and Tolerability of GalNAc3-Conjugated Antisense Drugs Compared to the Same-Sequence 2'-O-Methoxyethyl-Modified Antisense Drugs: Results from an Integrated Assessment of Phase 1 Clinical Trial Data.","authors":"Brenda F Baker, Shuting Xia, Wesley Partridge, Jeffery A Engelhardt, Sotirios Tsimikas, Stanley T Crooke, Sanjay Bhanot, Richard S Geary","doi":"10.1089/nat.2023.0026","DOIUrl":"10.1089/nat.2023.0026","url":null,"abstract":"The triantennary N-acetylgalactosamine (GalNAc3) cluster has demonstrated the utility of receptor-mediated uptake of ligand-conjugated antisense drugs targeting RNA expressed by hepatocytes. GalNAc3-conjugated 2'-O-methoxyethyl (2'MOE) modified antisense oligonucleotides (ASOs) have demonstrated a higher potency than the unconjugated form to support lower doses for an equivalent pharmacological effect. We utilized the Ionis integrated safety database to compare four GalNAc3-conjugated and four same-sequence unconjugated 2'MOE ASOs. This assessment evaluated data from eight randomized placebo-controlled dose-ranging phase 1 studies involving 195 healthy volunteers (79 GalNAc3 ASO, 24 placebo; 71 ASO, 21 placebo). No safety signals were identified by the incidence of abnormal threshold values in clinical laboratory tests for either ASO group. However, there was a significant increase in mean alanine transaminase levels compared with placebo in the upper dose range of the unconjugated 2'MOE ASO group. The mean percentage of subcutaneous injections leading to local cutaneous reaction was 30-fold lower in the GalNAc3-conjugated ASO group compared with the unconjugated ASO group (0.9% vs. 28.6%), with no incidence of flu-like reactions (0.0% vs. 0.7%). Three subjects (4.2%) in the unconjugated ASO group discontinued dosing. An improvement in the overall safety and tolerability profile of GalNAc3-conjugated 2'MOE ASOs is evident in this comparison of short-term clinical data in healthy volunteers.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"18-25"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reversible Aptamer Staining, Sorting, and Cleaning of Cells (Clean FACS) with Antidote Oligonucleotide or Nuclease Yields Fully Responsive Cells. 用解毒寡核苷酸或核酸酶对细胞进行可逆性色素染色、分选和清洁（清洁荧光激活细胞分选），产生完全响应的细胞。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-02-01 Epub Date: 2024-01-30 DOI: 10.1089/nat.2023.0050

Martin D Requena, Amy Yan, Telmo Llanga, Bruce A Sullenger

{"title":"Reversible Aptamer Staining, Sorting, and Cleaning of Cells (Clean FACS) with Antidote Oligonucleotide or Nuclease Yields Fully Responsive Cells.","authors":"Martin D Requena, Amy Yan, Telmo Llanga, Bruce A Sullenger","doi":"10.1089/nat.2023.0050","DOIUrl":"10.1089/nat.2023.0050","url":null,"abstract":"The ability to reverse the binding of aptamers to their target proteins has received considerable attention for developing controllable therapeutic agents. Recently, use of aptamers as reversible cell-sorting ligands has also sparked interest. Antibodies are currently utilized for isolating cells expressing a particular cell surface receptor. The inability to remove antibodies from isolated cells following sorting greatly limits their utility for many applications. Previously, we described how a particular aptamer-antidote oligonucleotide pair can isolate cells and clean them. Here, we demonstrate that this approach is generalizable; aptamers can simultaneously recognize more than one cell type during fluorescent activated cell sorting (FACS). Moreover, we describe a novel approach to reverse aptamer binding following cell sorting using a nuclease. This alternative strategy represents a cleaning approach that does not require the generation of antidote oligonucleotides for each aptamer and will greatly reduce the cost and expand the utility of Clean FACS.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"12-17"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acknowledgment of Reviewers 2023. 鸣谢 2023 年审稿人。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-02-01 Epub Date: 2023-12-14 DOI: 10.1089/nat.2023.29008.ack

引用次数: 0

Biodistribution of Radioactively Labeled Splice Modulating Antisense Oligonucleotides After Intracerebroventricular and Intrathecal Injection in Mice. 放射性标记的剪接调节反义寡核苷酸在小鼠脑室内和鞘内注射后的生物分布。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-02-01 DOI: 10.1089/nat.2023.0018

Tom Metz, Mick M Welling, Ernst Suidgeest, Esmée Nieuwenhuize, Thomas de Vlaam, Daniel Curtis, Tsinatkeab T Hailu, Louise van der Weerd, Willeke M C van Roon-Mom

{"title":"Biodistribution of Radioactively Labeled Splice Modulating Antisense Oligonucleotides After Intracerebroventricular and Intrathecal Injection in Mice.","authors":"Tom Metz, Mick M Welling, Ernst Suidgeest, Esmée Nieuwenhuize, Thomas de Vlaam, Daniel Curtis, Tsinatkeab T Hailu, Louise van der Weerd, Willeke M C van Roon-Mom","doi":"10.1089/nat.2023.0018","DOIUrl":"10.1089/nat.2023.0018","url":null,"abstract":"Antisense oligonucleotides (AONs) are promising therapeutic candidates, especially for neurological diseases. Intracerebroventricular (ICV) injection is the predominant route of administration in mouse studies, while in clinical trials, intrathecal (IT) administration is mostly used. There is little knowledge on the differences in distribution of these injection methods within the same species over time. In this study, we compared the distribution of splice-switching AONs targeting exon 15 of amyloid precursor protein pre-mRNA injected via the ICV and IT route in mice. The AON was labeled with radioactive indium-111 and mice were imaged using single-photon emission computed tomography (SPECT) 0, 4, 24, 48, 72, and 96 h after injection. In vivo SPECT imaging showed 111In-AON activity diffused throughout the central nervous system (CNS) in the first hours after injection. The 111In-AON activity in the CNS persisted over the course of 4 days, while signal in the kidneys rapidly decreased. Postmortem counting in different organs and tissues showed very similar distribution of 111In-AON activity throughout the body, while the signal in the different brain regions was higher with ICV injection. Overall, IT and ICV injection have very similar distribution patterns in the mouse, but ICV injection is much more effective in reaching the brain.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":"34 1","pages":"26-34"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiplexed In Vivo Screening Using Barcoded Aptamer Technology to Identify Oligonucleotide-Based Targeting Reagents. 利用条形码适配体技术进行多重体内筛选，以确定基于寡核苷酸的靶向试剂。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-01-01 Epub Date: 2024-05-16 DOI: 10.1089/nat.2024.0010

Brian J Thomas, Caitlyn Guldenpfennig, Mark A Daniels, Donald H Burke, David Porciani

{"title":"Multiplexed In Vivo Screening Using Barcoded Aptamer Technology to Identify Oligonucleotide-Based Targeting Reagents.","authors":"Brian J Thomas, Caitlyn Guldenpfennig, Mark A Daniels, Donald H Burke, David Porciani","doi":"10.1089/nat.2024.0010","DOIUrl":"10.1089/nat.2024.0010","url":null,"abstract":"Recent FDA approvals of mRNA vaccines, short-interfering RNAs, and antisense oligonucleotides highlight the success of oligonucleotides as therapeutics. Aptamers are excellent affinity reagents that can selectively label protein biomarkers, but their clinical application has lagged. When formulating a given aptamer for in vivo use, molecular design details can determine biostability and biodistribution; therefore, extensive postselection manipulation is often required for each new design to identify clinically useful reagents harboring improved pharmacokinetic properties. Few methods are available to comprehensively screen such aptamers, especially in vivo, constituting a significant bottleneck in the field. In this study, we introduce barcoded aptamer technology (BApT) for multiplexed screening of predefined aptamer formulations in vitro and in vivo. We demonstrate this technology by simultaneously investigating 20 aptamer formulations, each harboring different molecular designs, for targeting Non-Small Cell Lung Cancer cells and tumors. Screening in vitro identified a 45 kDa bispecific formulation as the best cancer cell targeting reagent, whereas screening in vivo identified a 30 kDa monomeric formulation as the best tumor-specific targeting reagent. The multiplexed analysis pipeline also identified biodistribution phenotypes shared among formulations with similar molecular architectures. The BApT approach we describe here has the potential for broad application to fields where oligonucleotide-based targeting reagents are desired.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"109-124"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antisense Oligonucleotide-Based Rescue of Complex Intronic Splicing Defects in ABCA4. 基于反义寡核苷酸的 ABCA4 复杂非线性剪接缺陷的修复。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-01-01 Epub Date: 2024-05-27 DOI: 10.1089/nat.2024.0008

Zelia Corradi, Rebekkah J Hitti-Malin, Laura A de Rooij, Alejandro Garanto, Rob W J Collin, Frans P M Cremers

{"title":"Antisense Oligonucleotide-Based Rescue of Complex Intronic Splicing Defects in ABCA4.","authors":"Zelia Corradi, Rebekkah J Hitti-Malin, Laura A de Rooij, Alejandro Garanto, Rob W J Collin, Frans P M Cremers","doi":"10.1089/nat.2024.0008","DOIUrl":"10.1089/nat.2024.0008","url":null,"abstract":"The ABCA4 gene, involved in Stargardt disease, has a high percentage of splice-altering pathogenic variants, some of which cause complex RNA defects. Although antisense oligonucleotides (AONs) have shown promising results in splicing modulation, they have not yet been used to target complex splicing defects. Here, we performed AON-based rescue studies on ABCA4 complex splicing defects. Intron 13 variants c.1938-724A>G, c.1938-621G>A, c.1938-619A>G, and c.1938-514A>G all lead to the inclusion of different pseudo-exons (PEs) with and without an upstream PE (PE1). Intron 44 variant c.6148-84A>T results in multiple PE inclusions and/or exon skipping events. Five novel AONs were designed to target these defects. AON efficacy was assessed by in vitro splice assays using midigenes containing the variants of interest. All screened complex splicing defects were effectively rescued by the AONs. Although varying levels of efficacy were observed between AONs targeting the same PEs, for all variants at least one AON restored splicing to levels comparable or better than wildtype. In conclusion, AONs are a promising approach to target complex splicing defects in ABCA4.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"125-133"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular Vesicles Loaded with Long Antisense RNAs Repress Severe Acute Respiratory Syndrome Coronavirus 2 Infection. 装载了长反义 RNA 的细胞外囊泡抑制了严重急性呼吸系统综合征冠状病毒 2 的感染。

IF 4 2区医学

Nucleic acid therapeutics Pub Date : 2024-01-01 Epub Date: 2024-03-26 DOI: 10.1089/nat.2023.0078

Adi Idris, Surya Shrivastava, Aroon Supramaniam, Roslyn M Ray, Galina Shevchenko, Dhruba Acharya, Nigel A J McMillan, Kevin V Morris

{"title":"Extracellular Vesicles Loaded with Long Antisense RNAs Repress Severe Acute Respiratory Syndrome Coronavirus 2 Infection.","authors":"Adi Idris, Surya Shrivastava, Aroon Supramaniam, Roslyn M Ray, Galina Shevchenko, Dhruba Acharya, Nigel A J McMillan, Kevin V Morris","doi":"10.1089/nat.2023.0078","DOIUrl":"10.1089/nat.2023.0078","url":null,"abstract":"Long antisense RNAs (asRNAs) have been observed to repress HIV and other virus expression in a manner that is refractory to viral evolution. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) disease, has a distinct ability to evolve resistance around antibody targeting, as was evident from the emergence of various SARS-CoV-2 spike antibody variants. Importantly, the effectiveness of current antivirals is waning due to the rapid emergence of new variants of concern, more recently the omicron variant. One means of avoiding the emergence of viral resistance is by using long asRNA to target SARS-CoV-2. Similar work has proven successful with HIV targeting by long asRNA. In this study, we describe a long asRNA targeting SARS-CoV-2 RNA-dependent RNA polymerase gene and the ability to deliver this RNA in extracellular vesicles (EVs) to repress virus expression. The observations presented in this study suggest that EV-delivered asRNAs are one means to targeting SARS-CoV-2 infection, which is both effective and broadly applicable as a means to control viral expression in the absence of mutation. This is the first demonstration of the use of engineered EVs to deliver long asRNA payloads for antiviral therapy.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"101-108"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0