Bioanalysis最新文献_第2页

Regulatory and scientific considerations in PK and biomarker assay validation: lessons from bioanalytical practice. PK和生物标志物测定验证中的监管和科学考虑：来自生物分析实践的经验教训。

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-02-01 Epub Date: 2026-04-16 DOI: 10.1080/17576180.2026.2658614

Ruwini D Rajapaksha, John T Farmer

{"title":"Regulatory and scientific considerations in PK and biomarker assay validation: lessons from bioanalytical practice.","authors":"Ruwini D Rajapaksha, John T Farmer","doi":"10.1080/17576180.2026.2658614","DOIUrl":"10.1080/17576180.2026.2658614","url":null,"abstract":"Bioanalytical method validation is a foundation of drug development, ensuring that pharmacokinetic (PK), toxicokinetic (TK), and biomarker assays produce accurate, precise, reliable, and decision-enabling data. Over the past several decades, advances in analytical technologies including ligand-binding assays (LBAs) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) platforms have transformed the field of bioanalysis. Regulatory guidance from the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the International Council for Harmonization (ICH) has evolved to reflect these advancements. This review provides a comprehensive comparison of PK and biomarker assay validation, highlighting critical parameters such as selectivity, sensitivity, calibration, accuracy, precision, dilution/parallelism, specificity, and stability. Best practice recommendations are provided for method development, qualification, and validation, with a focus on fit-for-purpose (FFP) approaches and context-of-use (CoU) considerations. Areas of ambiguity in current regulatory expectations for biomarker validations, common pitfalls encountered during regulatory interactions, and emerging trends in bioanalysis are also reviewed. This review paper aims to guide bioanalytical scientists in developing robust, compliant assays that support regulatory submissions and facilitate informed drug development decisions.","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":" ","pages":"293-311"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Comparative assessment of RT-dPCR and RT-qPCR for RNA quantification in IgG mRNA-lipid nanoparticle bioanalysis. RT-dPCR与RT-qPCR在IgG mrna -脂质纳米颗粒生物分析中RNA定量的比较评价。

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-02-01 Epub Date: 2026-04-30 DOI: 10.1080/17576180.2026.2664198

Zhihua Jiang, Julia Smith, Jessica Haskins, Brianna McPhee, Zhiping You, Dennis O'Rourke, Alison Joyce

{"title":"Comparative assessment of RT-dPCR and RT-qPCR for RNA quantification in IgG mRNA-lipid nanoparticle bioanalysis.","authors":"Zhihua Jiang, Julia Smith, Jessica Haskins, Brianna McPhee, Zhiping You, Dennis O'Rourke, Alison Joyce","doi":"10.1080/17576180.2026.2664198","DOIUrl":"10.1080/17576180.2026.2664198","url":null,"abstract":"Background: mRNA-LNP therapeutics have revolutionized drug development across various therapeutic areas, necessitating accurate and robust RNA quantification in bioanalysis. While RT-qPCR is commonly used for RNA quantification, RT-dPCR has emerged as an alternative, with enhanced precision and robustness. Yet, a systematic comparison of these methodologies for mRNA-LNP bioanalysis remains absent.Methods: Duplex RT-dPCR and RT-qPCR assays using identical primers and probes were developed to quantify LNP encapsulated IgG heavy chain (HC) and light chain (LC) RNA. Both assays analyzed RNA from 50 rat serum samples dosed with the mRNA-LNP compound, and results were statistically compared for measurement agreement and method reliability.Results: Both assays were qualified, meeting the pre-defined assay acceptance criteria. HC RNA quantification showed strong agreement between the two methods (Lin's CCC = 0.96). However, RT-qPCR significantly underestimated LC RNA levels compared to RT-dPCR, with a dPCR/qPCR ratio mean of 2.83, suggesting gene-dependent variability in quantification accuracy.Conclusion: This study provides a systematic evaluation of RT-dPCR and RT-qPCR in RNA quantification, advancing our understanding of their application in mRNA-LNP bioanalysis. These findings underscore the critical need for thorough assay evaluation to ensure reliable mRNA measurements, and prevent potential inaccuracies that could lead to misleading results in drug development and regulatory decision-making.","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":" ","pages":"279-292"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-02-01 Epub Date: 2026-04-30 DOI: 10.1080/17576180.2026.2664206

Khawla Abouhait, Ahmad Z Al Meslamani

{"title":"Biosimilars in practice: best-practice immunogenicity assessment and switching/interchangeability strategies for pharmacy-led programs.","authors":"Khawla Abouhait, Ahmad Z Al Meslamani","doi":"10.1080/17576180.2026.2664206","DOIUrl":"10.1080/17576180.2026.2664206","url":null,"abstract":"Wider access to biologic medicines has been made possible by biosimilars, which provide clinically equivalent options at a lower cost. However, robust immunogenicity surveillance and reliable switching and interchangeability pathways are still necessary for real-world use. The \"totality of evidence\" may be translated into standardized, patient-centered switching and interchangeability pathways that maintain efficacy and safety through pharmacy-led stewardship initiatives. This narrative review was carried out using PubMed/MEDLINE, Embase, Scopus, Web of Science Core Collection, and Google Scholar between 1 January 2019, and 1 December 2025. This review shows that biosimilars and reference biologics are clinically equivalent, and switching typically has no appreciable impact on population-level safety or immunogenicity. However, switching should be supported by a pharmacy-led toolkit that includes risk-stratified immunogenicity testing (event-triggered vs. scheduled), a minimum assay set plus drug levels, and an action algorithm to differentiate PK failure, PD failure, and immune-mediated failure because a small subset of patients may experience clinically significant ADA/NAb-mediated loss of response or tolerability issues. The issue is now to \"operate switching safely\" rather than \"prove switching,\" since regulatory trends encourage interchangeability and simplify evidence requirements.","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":" ","pages":"313-324"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Biochemical characterization of cerebrospinal fluid in leptomeningeal carcinomatosis and infectious meningitis using the metabolic product model: a diagnostic performance evaluation in a single-center retrospective cohort. 利用代谢产物模型对脑脊液在小脑膜癌和感染性脑膜炎中的生化特征进行评价：一项单中心回顾性队列的诊断性能评估

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-02-01 Epub Date: 2026-03-31 DOI: 10.1080/17576180.2026.2653859

Xianglei Li, Yanna Ning, Jiaoyang Xu, Biao Gao, Lina Huang, Yan Liu, Adi Idris

{"title":"Biochemical characterization of cerebrospinal fluid in leptomeningeal carcinomatosis and infectious meningitis using the metabolic product model: a diagnostic performance evaluation in a single-center retrospective cohort.","authors":"Xianglei Li, Yanna Ning, Jiaoyang Xu, Biao Gao, Lina Huang, Yan Liu, Adi Idris","doi":"10.1080/17576180.2026.2653859","DOIUrl":"10.1080/17576180.2026.2653859","url":null,"abstract":"Background: Leptomeningeal metastasis (LM) and infectious meningitis often present with similar neurological symptoms, making clinical differentiation challenging. We retrospectively analyzed cerebrospinal fluid (CSF) biochemistry (lactate (LAC), lactate dehydrogenase (LDH), protein, glucose) in patients with confirmed LM and infectious meningitis (bacterial or viral) to delineate characteristic metabolic profiles.Research design and methods: In this single-center retrospective cohort, we included 39 patients with cytology-confirmed LM, 38 with bacterial meningitis (BM), and 40 with viral meningitis (VM). We calculated an LDH × LAC product and compared its diagnostic performance to traditional biochemical markers using ROC analysis and DeLong tests for area under the curve differences.Results: The LDH×LAC index distinguished LM from VM and BM, outperforming the LDH/LAC ratio. Notably, 74.4% of LM patients had low CSF cell counts (≤50 × 106/L) and 66.7% had ≤20% tumor cells, yet LDH×LAC remained highly sensitive even in these low-burden cases.Conclusions: These findings highlight that certain biochemical signatures can distinguish etiologies whereby high CSF lactate favors bacterial infection or aggressive tumor involvement, whereas normal glucose and low lactate favor viral causes. Our results emphasize distinct CSF signatures in neoplastic compared to infectious meningitis, suggesting metabolic profiling can aid diagnosis.","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":" ","pages":"235-243"},"PeriodicalIF":1.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Correction. 修正。

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-01-19 DOI: 10.1080/17576180.2026.2619351

引用次数: 0

A simple and highly sensitive LC-MS/MS bioanalytical method for phosphorodiamidate morpholino oligonucleotides in plasma. 一种简便、高灵敏度的LC-MS/MS分析血浆中磷酸二酯寡核苷酸的方法。

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-01-01 Epub Date: 2026-02-19 DOI: 10.1080/17576180.2026.2632688

Tsubasa Kameyama, Shunji Imai, Rei Mitamura, Makoto Niwa, Tetsuhiro Yamada, Kazutomi Kusano

{"title":"A simple and highly sensitive LC-MS/MS bioanalytical method for phosphorodiamidate morpholino oligonucleotides in plasma.","authors":"Tsubasa Kameyama, Shunji Imai, Rei Mitamura, Makoto Niwa, Tetsuhiro Yamada, Kazutomi Kusano","doi":"10.1080/17576180.2026.2632688","DOIUrl":"10.1080/17576180.2026.2632688","url":null,"abstract":"Background: LC-MS/MS is widely used for the quantification of phosphorodiamidate morpholino oligomers, but its low sensitivity is a problem. In addition, solid-phase extraction, a pretreatment method generally used for LC-MS/MS analysis, results in low recovery when applied to phosphorodiamidate morpholino oligomers. Therefore, a highly sensitive bioanalytical method for the determination of phosphorodiamidate morpholino oligomers using LC-MS/MS with improved pretreatment is desired.Results: Protein precipitation was applied to LC-MS/MS analysis for viltolarsen, as a typical phosphorodiamidate morpholino oligomer, in plasma, and PPT with MeOH achieved high recoveries (>90%). Reversed-phase liquid chromatography (RPLC) with gradient elution improved ion suppression compared to hydrophilic interaction liquid chromatography. A combination of PPT and RPLC achieved higher sensitivity (lower limit of quantification, 1 ng/mL) than those of approved phosphorodiamidate morpholino oligomers (10 to 20 ng/mL in their clinical reviews), and the between-run accuracy and precision ranged from 97.1% to 109% and 2.56% to 10.5%, respectively. This method was also shown to be applicable to another phosphorodiamidate morpholino oligomer, ψM23D (+07-18).Conclusion: A simple and highly sensitive bioanalytical method for the determination of viltolarsen was established by optimizing RPLC and PPT, and the method was successfully applied to a phosphorodiamidate morpholino oligomers with a different sequence.","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":" ","pages":"133-145"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Implementation of the fully automated diagnostic immunoanalyzer cobas e411 in the bioanalytical laboratory - Lessons learnt. 全自动诊断免疫分析仪cobas e411在生物分析实验室的实施-经验教训。

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-01-01 Epub Date: 2026-02-18 DOI: 10.1080/17576180.2026.2629504

Thomas Emrich, Eginhard Schick, Andreas Wolfert, Julian Meir, Xiaoying Guo, Pavel Kubalec, Kay G Stubenrauch, Katharina Ockenga, Martina Reis-Dybowski, Stephanie Vauleon, Julia Heinrich, Matthew Barfield, Roland F Staack

{"title":"Implementation of the fully automated diagnostic immunoanalyzer cobas e411 in the bioanalytical laboratory - Lessons learnt.","authors":"Thomas Emrich, Eginhard Schick, Andreas Wolfert, Julian Meir, Xiaoying Guo, Pavel Kubalec, Kay G Stubenrauch, Katharina Ockenga, Martina Reis-Dybowski, Stephanie Vauleon, Julia Heinrich, Matthew Barfield, Roland F Staack","doi":"10.1080/17576180.2026.2629504","DOIUrl":"10.1080/17576180.2026.2629504","url":null,"abstract":"Aims: This study assessed the automated cobas e411 immunoanalyzer as a high-efficiency alternative to manual ELISA for pharmacokinetic and pharmacodynamic analyses. Key objectives included reducing manual resource burdens and minimizing analyst-dependent variability while achieving analytical performance comparable or superior to established ELISA standards.Materials & methods: To achieve GLP and FDA 21 CFR Part 11 and 58 compliance, a dedicated \"Elecsys system\", comprising the off-the-shelf cobas e411 platform and an in-house developed software package (CoLiBri) for instrument control and LIMS connection was subjected to Computerized System Validation (CSV). The Elecsys system's analytical performance was compared directly to ELISA. Robustness was further assessed through clinical sample analysis and free analyte quantification in biological matrices.Results: The cobas e411 demonstrated comparable sensitivity and precision to ELISA while offering a significantly wider dynamic range due to electrochemiluminescence readout. Automation minimized human error and enabled high-throughput singlicate analysis, a capability unattainable with manual methods. Validation of numerous non-clinical and clinical assays and routine sample analyses confirmed platform's efficiency and ability to provide rapid turnaround for bioanalysis.Conclusions: The Elecsys system is a robust, GLP-compliant platform that streamlines bioanalytical workflows. By automating labor-intensive steps, it significantly enhances data quality and efficiency compared to traditional manual ligand-binding assays.","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":" ","pages":"77-89"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The dynamic changes of serum levels of PD-1/PD-L1 correlate with the therapeutic effectiveness of antibiotics in patients with sepsis. 脓毒症患者血清PD-1/PD-L1水平的动态变化与抗生素治疗效果相关。

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-01-01 Epub Date: 2026-02-28 DOI: 10.1080/17576180.2026.2637733

Yan Li, Biran Ding, Lei Ye, Yuanbao Xu

{"title":"The dynamic changes of serum levels of PD-1/PD-L1 correlate with the therapeutic effectiveness of antibiotics in patients with sepsis.","authors":"Yan Li, Biran Ding, Lei Ye, Yuanbao Xu","doi":"10.1080/17576180.2026.2637733","DOIUrl":"10.1080/17576180.2026.2637733","url":null,"abstract":"Background: Sepsis-induced immunosuppression is a significant contributor to mortality, with the programmed cell death protein 1 and its ligand (PD-1/PD-L1) pathway playing a central role in T-cell exhaustion. While their dynamics as biomarkers for monitoring treatment response in specific infections, such as Enterobacteriaceae-induced sepsis, remain unclear.Materials and methods: This study enrolled 63 patients with Enterobacteriaceae septicemia and 59 healthy controls. Serum levels of sPD-1/sPD-L1 were quantified at admission (Day 0) and on Days 3, 7, and 14. Patients were stratified into responders and non-responders based on clinical outcomes.Results: At Day 0, sepsis patients had significantly higher levels of sPD-1 and sPD-L1 compared to healthy controls (p < 0.001). Longitudinal analysis revealed that patients who responded favorably to treatment exhibited a significant progressive decline in both biomarkers over the 14-day period. In contrast, non-responders maintained persistently elevated levels. Furthermore, initial sPD-1/sPD-L1 concentrations positively correlated with SOFA score, lactate level and PCT level. Furthermore, the analysis showed that the antibiotics β-lactam/β-lactamase inhibitor and carbapenem might not directly influence the sPD-1/sPD-L1 levels.Conclusion: Serum sPD-1 and sPD-L1 levels are significantly elevated in Enterobacteriaceae sepsis and dynamically decreased in patients responding to therapy. These findings underscore their potential as valuable prognostic biomarkers for monitoring immune reconstitution and treatment efficacy.","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":" ","pages":"159-167"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Progress and promise of pharmacodynamic biomarkers: novel strategies and assay considerations in drug development. 药效学生物标志物的进展和前景：药物开发中的新策略和分析考虑。

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-01-01 Epub Date: 2026-03-10 DOI: 10.1080/17576180.2026.2624362

Carmen Fernández-Metzler, Karen J Quadrini, Lakshmi Amaravadi, Stephanie Cape, Jennifer Green, Amanda Hays, Jurre J Kamphorst, Sreenivas Laxmanan, Alok Pandey, Xiazi Qiu, Ruwini D Rajapaksha, Mohamed Hassanein

{"title":"Progress and promise of pharmacodynamic biomarkers: novel strategies and assay considerations in drug development.","authors":"Carmen Fernández-Metzler, Karen J Quadrini, Lakshmi Amaravadi, Stephanie Cape, Jennifer Green, Amanda Hays, Jurre J Kamphorst, Sreenivas Laxmanan, Alok Pandey, Xiazi Qiu, Ruwini D Rajapaksha, Mohamed Hassanein","doi":"10.1080/17576180.2026.2624362","DOIUrl":"10.1080/17576180.2026.2624362","url":null,"abstract":"Pharmacodynamic (PD) biomarkers provide crucial insights into a drug's mechanism of action (MoA) and efficacy by measuring its effects on biological targets within an organism. PD biomarkers can be proximal (e.g. receptor occupancy, enzyme inhibition) or distal (e.g. downstream pathway modulation) to the biological target. In drug development, PD biomarkers are essential for monitoring patient response, assessing therapeutic efficacy, optimizing dosage strategies, and streamlining the drug development process by informing go/no-go decisions. In personalized medicine, PD biomarkers enable tailored treatments based on individual responses, enhancing both effectiveness and safety. Sound bioanalytical strategies and rigorous assay validation practices are key for successful integration of PD biomarkers into clinical trials. This paper outlines the bioanalytical and assay considerations for developing and validating informative PD biomarker assays and their use in drug development.","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":" ","pages":"91-109"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Harmonizing immunogenicity for AAV and LNP/mRNA modalities: best-practice panels for binding, neutralizing, and cellular assays with pre-existing immunity controls. 协调AAV和LNP/mRNA模式的免疫原性：结合、中和和预先存在免疫控制的细胞测定的最佳实践面板。

IF 1.8 4区医学

Bioanalysis Pub Date : 2026-01-01 Epub Date: 2026-02-28 DOI: 10.1080/17576180.2026.2638522

Ahmad Z Al Meslamani, Anan S Jarab, Eman Merghani Ali Mohammed

{"title":"Harmonizing immunogenicity for AAV and LNP/mRNA modalities: best-practice panels for binding, neutralizing, and cellular assays with pre-existing immunity controls.","authors":"Ahmad Z Al Meslamani, Anan S Jarab, Eman Merghani Ali Mohammed","doi":"10.1080/17576180.2026.2638522","DOIUrl":"10.1080/17576180.2026.2638522","url":null,"abstract":"Introduction: Immunogenicity remains the principal constraint on the efficacy, safety, and re-dosing of adeno-associated virus (AAV) and lipid nanoparticle (LNP) - mRNA therapeutics. Clinical decision-making and comparability between programs are hampered by heterogeneous test formats and matrix effects.Areas covered: This narrative review integrates 2023-2025 bench, translational, clinical, and regulatory evidence. Studies on binding, neutralizing, and cellular/innate tests, anti-PEG epidemiology, complement biology, and ultrasensitive digital immunoassays were identified through searches of PubMed, Web of Science, Google Scholar, and regulatory archives. We propose a panel with tiers: Tier-0 pre-screening using isotype-resolved anti-PEG and total anti-capsid; Tier-1 standardized cell-based transduction inhibition with an optional constant-serum-concentration design to reduce dilution-induced matrix bias; Tier-2 mechanistic cellular and innate panels (e.g. complement split products, cytokines, and capsid-specific T-cell assays); and Tier-3 attomolar digital assays for critical biomarkers.Future perspective: By implementing this harmonized, matrix-aware panel, which is presented as a fit-for-purpose analytical best-practice proposal rather than an evidence-validated clinical standard, screening-failure bias can be minimized, eligibility criteria can be stabilized, and connections between assay results and dosing, monitoring, and re-dosing/deferral may be strengthened.","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":" ","pages":"199-215"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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