Nucleic acid therapeutics最新文献

Incorporation of a pH-Sensitive Linker into Lipid-ASO Conjugates Drives Increased Endosomal Membrane Remodeling Events. 在脂质- aso偶联物中加入ph敏感连接物可增加内体膜重构事件。

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-12-01 Epub Date: 2026-09-22 DOI: 10.1177/21593337261488803

Priyanka Mangla, Emma Kay, Michael J Munson, Daniel van Leeuwen, Kathrin Stavenhagen, Smita Nahar, Annabelle Biscans

{"title":"Incorporation of a pH-Sensitive Linker into Lipid-ASO Conjugates Drives Increased Endosomal Membrane Remodeling Events.","authors":"Priyanka Mangla, Emma Kay, Michael J Munson, Daniel van Leeuwen, Kathrin Stavenhagen, Smita Nahar, Annabelle Biscans","doi":"10.1177/21593337261488803","DOIUrl":"10.1177/21593337261488803","url":null,"abstract":"Oligonucleotide therapeutics have great potential for the treatment of previously \"undruggable\" human diseases; however, their broad utility is limited by challenges in delivery and achieving sufficient endosomal escape. Systemic delivery of antisense oligonucleotides (ASOs) results in their primary accumulation in the liver and kidneys, limiting their effectiveness in targeting RNAs in other tissues. Conjugation to specific lipids has been employed to boost productive delivery of oligonucleotides to nonhepatic tissues such as heart and skeletal muscle. Once oligonucleotides have entered the right cell type, they then need to escape the endosomal lipid bilayer to reach their RNA targets in the nucleus and cytoplasm. In this article, we show that introducing a pH-sensitive linker in C16 lipid- and C22 lipid-conjugated ASOs increases endosomal remodeling events detected via a Galectin 9 reporter imaging assay, despite similar levels of ASO cellular uptake. Furthermore, incorporation of a pH-sensitive linker can lead to improved gene silencing in vitro. These data suggest that decoupling the lipid from the ASO is a promising approach to improve ASO endosomal escape and activity. Therefore, pH-sensitive linkers offer a novel strategy to expand the potential use of oligonucleotide therapeutics.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"287-299"},"PeriodicalIF":4.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025510","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

Nucleic Acid Therapeutics in an Age of Artificial Intelligence. 人工智能时代的核酸疗法。

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-12-01 Epub Date: 2026-10-15 DOI: 10.1177/21593337261496161

David R Corey

引用次数: 0

rHuPH20 Enhances Extravascular Delivery of mRNA Lipid Nanoparticles in Mice and Minipigs. rHuPH20增强小鼠和迷你猪的mRNA脂质纳米颗粒血管外递送

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-12-01 Epub Date: 2026-08-12 DOI: 10.1177/21593337261479163

Ryan P Nolan, Marie A Printz, David W Kang, Robert J Connor, Yan Wang, Limin Liu, Chris Wahl

{"title":"rHuPH20 Enhances Extravascular Delivery of mRNA Lipid Nanoparticles in Mice and Minipigs.","authors":"Ryan P Nolan, Marie A Printz, David W Kang, Robert J Connor, Yan Wang, Limin Liu, Chris Wahl","doi":"10.1177/21593337261479163","DOIUrl":"10.1177/21593337261479163","url":null,"abstract":"Extravascular administration of mRNA lipid nanoparticles (mRNA-LNPs) offers practical and clinical advantages but is limited by tissue barriers that restrict dispersion, lymphatic access, systemic exposure, and ultimately, target tissue expression. Recombinant human hyaluronidase PH20 (rHuPH20) transiently modifies the hyaluronan-rich extracellular matrix in the subcutaneous (SC) space, enhancing SC delivery of protein therapeutics; however, its effect on mRNA-LNP delivery has not been systematically evaluated. Here, the impact of rHuPH20 on extravascular mRNA-LNP delivery was assessed across routes of administration and formulations. In a coordinated series of mouse and minipig studies, mRNA-LNP expression, biodistribution, lymphatic trafficking, systemic exposure, tissue deposition, and inflammatory responses were evaluated following SC, intramuscular (IM), and intravenous (IV) administration. In mice, co-administration with rHuPH20 increased local expression after IM dosing of luciferase mRNA-LNPs up to 7-fold and whole-body expression after SC dosing up to 38-fold, relative to the corresponding route without rHuPH20. In minipigs, rHuPH20-enabled SC administration of huEPO mRNA-LNPs produced serum huEPO exposure that approached IV benchmarks. rHuPH20 also increased hepatic expression following extravascular delivery, demonstrated consistent effects across ionizable lipid chemistries, and was associated with reduced pro-inflammatory cytokine responses following repeat-dosing. Collectively, these findings support rHuPH20 as an effective enabler of extravascular mRNA-LNP delivery.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"300-309"},"PeriodicalIF":4.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726018","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

Antisense Oligonucleotides that Are Toxic to Prion-Infected Mice Share an Emergent Mechanism. 对朊病毒感染小鼠具有毒性的反义寡核苷酸共享一个紧急机制。

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-12-01 Epub Date: 2026-10-10 DOI: 10.1177/21593337261494829

Hien T Zhao, Jill O'Moore, Daniel A Sprague, Juliana E Gentile, Sagar Damle, Briana Noble, Taylor L Corridon, Simone Lord, Jason Le, Samantha Graffam, Michael Howard, Kendrick DeSouza-Lenz, Hongda Li, John Matson, Susan Li, Stephanie Klein, Tyler Caron, Alissa A Coffey, Sonia M Vallabh, Holly B Kordasiewicz, Andrea Grindeland Panter, Eric Vallabh Minikel

{"title":"Antisense Oligonucleotides that Are Toxic to Prion-Infected Mice Share an Emergent Mechanism.","authors":"Hien T Zhao, Jill O'Moore, Daniel A Sprague, Juliana E Gentile, Sagar Damle, Briana Noble, Taylor L Corridon, Simone Lord, Jason Le, Samantha Graffam, Michael Howard, Kendrick DeSouza-Lenz, Hongda Li, John Matson, Susan Li, Stephanie Klein, Tyler Caron, Alissa A Coffey, Sonia M Vallabh, Holly B Kordasiewicz, Andrea Grindeland Panter, Eric Vallabh Minikel","doi":"10.1177/21593337261494829","DOIUrl":"10.1177/21593337261494829","url":null,"abstract":"Some, but not all, gapmer antisense oligonucleotides (ASOs) delivered into cerebrospinal fluid exhibit fatal subacute toxicity in late-stage prion-infected mice but not in uninfected mice. Here, we performed a battery of in vivo studies demonstrating that the toxicity is compound- and disease- stage-dependent, and not predicted by behavioral or molecular measurements in uninfected animals. A panel of toxic ASOs all elicited a consistent transcriptomic response signature in prion-infected mice, which emerged over the course of 7 days post dose. This signature, driven chiefly by decreased expression of a specific set of astrocyte-expressed genes, was absent in uninfected mice receiving the same ASOs, was absent, less intense, and/or more transient in infected mice receiving tolerated ASOs, and was distinct from the transcriptomic effect of prion disease itself. Our data argue that the toxicity is an interaction between ASO and prion disease at high doses for specific compounds, and does not represent an exacerbation of ASO toxicity nor of prion disease.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"275-286"},"PeriodicalIF":4.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148325","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

Improved Efficacy and Tolerability of Antisense Oligonucleotide with Guanidine-Bridged Nucleic Acid. 用胍桥接核酸提高反义寡核苷酸的疗效和耐受性。

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-10-29 DOI: 10.1177/21593337261502560

Takaaki Kawanobe, Ajaya Ram Shrestha, Hideaki Tomita

引用次数: 0

Considerations of Gene Expression Analysis Methods for Gapmer Antisense Oligonucleotide-Treated Samples. Gapmer反义寡核苷酸处理样品基因表达分析方法的思考。

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-10-25 DOI: 10.1177/21593337261497131

Christiana Wang, Shenglan Li, Jefferson C Sinson, Kristina Macakova, Gladys E Zapata, Jasmine O Brown, Nhi Ho, Pengfei Liu

{"title":"Considerations of Gene Expression Analysis Methods for Gapmer Antisense Oligonucleotide-Treated Samples.","authors":"Christiana Wang, Shenglan Li, Jefferson C Sinson, Kristina Macakova, Gladys E Zapata, Jasmine O Brown, Nhi Ho, Pengfei Liu","doi":"10.1177/21593337261497131","DOIUrl":"https://doi.org/10.1177/21593337261497131","url":null,"abstract":"Probe-based PCR assays are commonly used to evaluate gene expression in antisense oligonucleotide (ASO)-treated samples, but assay design and postextraction processing may introduce substantial measurement bias. We investigated workflow-dependent differences in measured knockdown across PCR-based and RNA-sequencing assays using an allele-specific gapmer ASO, targeting a linked single nucleotide polymorphism of a dominant-negative SPTAN1 variant. Exogenous ribonuclease H (RNase H) activity during reverse transcription or ribosomal RNA (rRNA)-depletion inflated apparent knockdown and reduced RNA-sequencing coverage at the ASO-binding site. In droplet digital PCR (ddPCR), allele-specific detection probes overlapping the ASO-binding site produced substantially greater apparent knockdown than nonoverlapping probes, particularly following workflows with active RNase H. Spike-in experiments showed that this bias was not reproduced by adding ASO to purified RNA before complementary DNA (cDNA) synthesis or to cDNA before ddPCR, but emerged when ASO was present during rRNA depletion. Together, these findings show that exogenous RNase H activity during RNA processing and ASO-probe overlap can distort measurements of gapmer-mediated transcript reduction. Poly(A)-based RNA sequencing, reverse transcriptase with reduced RNase H activity, and nonoverlapping PCR detection probes can minimize measurement bias when evaluating gapmer ASO-mediated knockdown.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"21593337261497131"},"PeriodicalIF":4.5,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271311","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

Nonclinical Development of Oligonucleotide-Based Therapeutics: Insights from an IQ DruSafe ONT Working Group Survey. 基于寡核苷酸的治疗方法的非临床发展：来自IQ drugafe ONT工作组调查的见解。

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-10-08 DOI: 10.1177/21593337261494828

Tod A Harper, Yi Yang, Sucheta Mukherjee, Marie Coeffet, Katja A Matheis, Alan Brown, Joel D Parry, Patrik Andersson, Onyi N Irrechukwu, Michaël Maes, Marc F DeCristofaro, Daniella M Pizzurro, Meredith Crosby, Jennifer D Sisler

{"title":"Nonclinical Development of Oligonucleotide-Based Therapeutics: Insights from an IQ DruSafe ONT Working Group Survey.","authors":"Tod A Harper, Yi Yang, Sucheta Mukherjee, Marie Coeffet, Katja A Matheis, Alan Brown, Joel D Parry, Patrik Andersson, Onyi N Irrechukwu, Michaël Maes, Marc F DeCristofaro, Daniella M Pizzurro, Meredith Crosby, Jennifer D Sisler","doi":"10.1177/21593337261494828","DOIUrl":"https://doi.org/10.1177/21593337261494828","url":null,"abstract":"Oligonucleotide-based therapeutics (ONTs) present unique nonclinical development challenges that are not fully addressed by paradigms established for small molecule pharmaceuticals or biologic therapeutics. To better understand current industry practice, the IQ DruSafe ONT Working Group conducted an industry survey examining species selection and high-dose selection in GLP repeat-dose toxicology studies, parameters used to determine safety margins, and human equivalent dose (HED) scaling used to support initial dose selection for first-in-human studies. Twenty companies provided responses, largely reflecting experience with systemically administered siRNA and RNase H antisense ONTs. Common themes identified in the survey included frequent use of both rodent and non-rodent species, with nonhuman primates used extensively, and high-dose selection based on an integrated consideration of maximum tolerated dose, pharmacodynamic response, and exposure-based criteria. Safety margins were most often based on steady-state exposure, generally using plasma rather than tissue exposure. For HED scaling, body surface area was the predominant approach, although some respondents reported use of body weight- or platform-informed alternatives. Overall, the survey identifies areas of convergence in current ONT nonclinical practice while highlighting unresolved areas where nonclinical practices diverge. The survey also identified areas where future ONT-specific regulatory guidance could improve consistency across ONT development programs.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"21593337261494828"},"PeriodicalIF":4.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128347","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

Embryo-Fetal Development and Maternal-Fetal Exposure of the Von Willebrand Factor Binding Aptamer Rondaptivon Pegol (BT200) in Rabbits. 家兔血管性血友病因子结合适配体ronadaptivon Pegol （BT200）的胎胚发育及母胎暴露

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-10-01 Epub Date: 2026-08-11 DOI: 10.1177/21593337261476421

Katarina D Kovacevic Miljević, Shuhao Zhu, James C Gilbert, Warren Harvey, Paul Tarantino, Bernd Jilma

{"title":"Embryo-Fetal Development and Maternal-Fetal Exposure of the Von Willebrand Factor Binding Aptamer Rondaptivon Pegol (BT200) in Rabbits.","authors":"Katarina D Kovacevic Miljević, Shuhao Zhu, James C Gilbert, Warren Harvey, Paul Tarantino, Bernd Jilma","doi":"10.1177/21593337261476421","DOIUrl":"10.1177/21593337261476421","url":null,"abstract":"Rondaptivon pegol (BT200) is a PEGylated RNA aptamer that prolongs von Willebrand factor (VWF) and factor VIII half-lives in patients with hemophilia A and von Willebrand disease (VWD) type 2B. Embryo-fetal safety is particularly relevant given the disproportionate disease burden in women with VWD. Data on placental transfer and developmental safety of PEGylated aptamers remain limited. An embryo-fetal development study was conducted in pregnant rabbits. Animals received rondaptivon pegol subcutaneously (0, 1.5, 5, or 15 mg/kg/day) from gestational days (GDs) 7-19. Maternal toxicokinetic samples and pooled fetal plasma concentrations were collected during gestation to quantify transplacental exposure. Rondaptivon pegol was well tolerated, with no maternal toxicity, no effects on implantation, and no treatment-related fetal malformations. Dose-related reductions in mean fetal body weight (<11%) were considered adverse only at the highest dose level. Maternal systemic exposure was supratherapeutic, with mean Cmax ranging from 133 to 807 µg/mL on GD19, far exceeding the human target concentration (∼1.2 µg/mL). Fetal plasma concentrations were <0.25% of maternal levels across all dose groups, confirming minimal placental transfer. The no-observed-adverse-effect level was 5 mg/kg/day. At maternal systemic exposures ranging from 110- to 670-fold above anticipated clinical levels, rondaptivon pegol did not adversely affect implantation, embryonic viability, or fetal development. These findings provide the first quantitative maternal-fetal pharmacokinetic and developmental safety data for a PEGylated aptamer, supporting further clinical evaluation of rondaptivon pegol in women of reproductive age.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"221-231"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707471","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

Biodistribution of Phosphorothioate-Based Antisense Oligonucleotides in Stabilin Receptor Knock-Out Models. 基于硫代磷酸酯的反义寡核苷酸在稳定受体敲除模型中的生物分布。

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-10-01 Epub Date: 2026-08-03 DOI: 10.1177/21593337261473078

Linda B Pratt, Abby E Bopp, Edward N Harris

{"title":"Biodistribution of Phosphorothioate-Based Antisense Oligonucleotides in Stabilin Receptor Knock-Out Models.","authors":"Linda B Pratt, Abby E Bopp, Edward N Harris","doi":"10.1177/21593337261473078","DOIUrl":"10.1177/21593337261473078","url":null,"abstract":"Phosphorothioate-based antisense oligonucleotides (PS-ASO) are a common class of ASO for therapeutic uses due to their resistance to nucleases and known deposition in human physiological systems. On the molecular level, these ASOs are recognized by several scavenger receptors, including scavenger receptors A and B (SR-A, SR-B) and Stabilin receptors, Stab1 and Stab2. The Stabilins bind and internalize a host of endogenous and exogenous molecules with high endocytic rates and low turnover times. To determine their specific role in the biodistribution of PS-ASOs, we intravascularly injected knockout (KO) mice for Stab1, Stab2 or Stab1Stab2 double KO (DKO). Our results show that each receptor contributes to PS-ASO clearance from the blood and accumulation in liver and spleen, locations where these receptors have the highest levels of expression. Moreover, Stab2 is the primary clearance receptor taking up the bulk of the PS-ASO found in blood. Our conclusion is that Stabilins have a profound effect on the catabolism of PS-ASOs, for which internalization and clearance from the tissue need to be taken into consideration in the design of any therapeutic ASO.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"244-252"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670093","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

Evaluation of Antisense Oligonucleotide-Associated Neuronal Lysosomal Changes. 反义寡核苷酸相关神经元溶酶体变化的评价。

IF 4.5 2区医学

Nucleic acid therapeutics Pub Date : 2026-10-01 Epub Date: 2026-08-06 DOI: 10.1177/21593337261473518

Albert A Mondragon, Kirk W Donovan, Xiaoping Hronowski, Susanne E Swalley, Sarah Lamore, Benbo Gao, Ramiro Massol, Martin Lamb, Branka Grubor, William Meier, Jim Fikes

{"title":"Evaluation of Antisense Oligonucleotide-Associated Neuronal Lysosomal Changes.","authors":"Albert A Mondragon, Kirk W Donovan, Xiaoping Hronowski, Susanne E Swalley, Sarah Lamore, Benbo Gao, Ramiro Massol, Martin Lamb, Branka Grubor, William Meier, Jim Fikes","doi":"10.1177/21593337261473518","DOIUrl":"10.1177/21593337261473518","url":null,"abstract":"Antisense oligonucleotides (ASOs) are a rapidly growing therapeutic modality that directly modulate splicing or expression of disease-causing genes. ASOs are internalized through various endocytic mechanisms that converge on the endolysosomal pathway. Our work here aims to evaluate changes to the endolysosomal system following repeated ASO exposure. Histological examinations of nonhuman primates following repeated intrathecal administration of ASOs reveal dose-related neuronal microvesicular vacuolation in the hippocampus, cortex, and spinal cord. These changes are not associated with any neuronal degenerative changes or glial activation. Examination by electron microscopy reveals lysosomes containing stacked membranous material. We established an induced pluripotent stem cell-derived motor neuron (iPSC-MN) model that recapitulates these lysosome changes. ASO exposure did not cause any changes in iPSC-MN viability. To characterize lysosomal changes, we isolated lysosomes from iPSC-MNs after ASO treatment and quantified their protein and lipid contents by liquid chromatography-mass spectrometry. Our lipidomics studies documented increases in bis(monoacylglycerol)phosphate and lactosylceramide following ASO administration; proteomic analysis showed changes in several proteins, including decreases in four lysosomal hydrolases (Carboxypeptidase Q, ß-galactosidase, Cathepsin A, and α-l-Fucosidase). Altogether, this work advances our understanding of the cellular consequences following prolonged ASO administration and may guide further investigations to characterize these effects.","PeriodicalId":19412,"journal":{"name":"Nucleic acid therapeutics","volume":" ","pages":"232-243"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679393","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