Alexander Kozikowski, Qing Wang, Cheng Yang, Neil Gordon, Kristina M Ciociola, Asanka Yapa, Claudia Villa, Paul Lambotte, Thomas Pisani, Javan Esfandiari, Angelo H Gunasekera
{"title":"基因治疗候选药物中AAV8结合抗体的快速检测:一种即时护理方法的发展。","authors":"Alexander Kozikowski, Qing Wang, Cheng Yang, Neil Gordon, Kristina M Ciociola, Asanka Yapa, Claudia Villa, Paul Lambotte, Thomas Pisani, Javan Esfandiari, Angelo H Gunasekera","doi":"10.1038/s41434-025-00559-0","DOIUrl":null,"url":null,"abstract":"<p><p>Preexisting anti-AAV antibodies pose a significant challenge to the success of Adeno-associated Virus (AAV) mediated gene therapies, as they can diminish therapeutic effectiveness, restrict patient eligibility for treatment, and cause serious health issues during treatment. This study introduces the first point-of-care (POC) test for the rapid, quantitative detection of AAV8 binding antibodies in patients' plasma, serum, and blood, leveraging Chembio's Dual Path Platform (DPP) technology. The DPP AAV8 Total Antibody (TAb) assay delivers results within 20 min from sample addition, with a dynamic range of 0-32 µg/ml when evaluated with purified human polyclonal antibodies that bind to AAV8, with reasonable specificity and sensitivity relative to Chembio's AAV8 TAb ELISA (R² = 0.90). Moreover, the assay demonstrated strong correlations with Chembio's AAV8 neutralizing antibody (NAb) ELISA and cell-based NAb assays (R² = 0.97 in plasma) (Cell-based assay adapted from BioAgilytix EU protocol). This rapid and reliable test can facilitate the screening of potential gene therapy patients for pre-existing antibodies that bind to AAV8 and assess their suitability for AAV8-mediated gene therapy.</p>","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rapid detection of AAV8 binding antibodies in gene therapy candidates: development of a point-of-care approach.\",\"authors\":\"Alexander Kozikowski, Qing Wang, Cheng Yang, Neil Gordon, Kristina M Ciociola, Asanka Yapa, Claudia Villa, Paul Lambotte, Thomas Pisani, Javan Esfandiari, Angelo H Gunasekera\",\"doi\":\"10.1038/s41434-025-00559-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Preexisting anti-AAV antibodies pose a significant challenge to the success of Adeno-associated Virus (AAV) mediated gene therapies, as they can diminish therapeutic effectiveness, restrict patient eligibility for treatment, and cause serious health issues during treatment. This study introduces the first point-of-care (POC) test for the rapid, quantitative detection of AAV8 binding antibodies in patients' plasma, serum, and blood, leveraging Chembio's Dual Path Platform (DPP) technology. The DPP AAV8 Total Antibody (TAb) assay delivers results within 20 min from sample addition, with a dynamic range of 0-32 µg/ml when evaluated with purified human polyclonal antibodies that bind to AAV8, with reasonable specificity and sensitivity relative to Chembio's AAV8 TAb ELISA (R² = 0.90). Moreover, the assay demonstrated strong correlations with Chembio's AAV8 neutralizing antibody (NAb) ELISA and cell-based NAb assays (R² = 0.97 in plasma) (Cell-based assay adapted from BioAgilytix EU protocol). This rapid and reliable test can facilitate the screening of potential gene therapy patients for pre-existing antibodies that bind to AAV8 and assess their suitability for AAV8-mediated gene therapy.</p>\",\"PeriodicalId\":12699,\"journal\":{\"name\":\"Gene Therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gene Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41434-025-00559-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41434-025-00559-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Rapid detection of AAV8 binding antibodies in gene therapy candidates: development of a point-of-care approach.
Preexisting anti-AAV antibodies pose a significant challenge to the success of Adeno-associated Virus (AAV) mediated gene therapies, as they can diminish therapeutic effectiveness, restrict patient eligibility for treatment, and cause serious health issues during treatment. This study introduces the first point-of-care (POC) test for the rapid, quantitative detection of AAV8 binding antibodies in patients' plasma, serum, and blood, leveraging Chembio's Dual Path Platform (DPP) technology. The DPP AAV8 Total Antibody (TAb) assay delivers results within 20 min from sample addition, with a dynamic range of 0-32 µg/ml when evaluated with purified human polyclonal antibodies that bind to AAV8, with reasonable specificity and sensitivity relative to Chembio's AAV8 TAb ELISA (R² = 0.90). Moreover, the assay demonstrated strong correlations with Chembio's AAV8 neutralizing antibody (NAb) ELISA and cell-based NAb assays (R² = 0.97 in plasma) (Cell-based assay adapted from BioAgilytix EU protocol). This rapid and reliable test can facilitate the screening of potential gene therapy patients for pre-existing antibodies that bind to AAV8 and assess their suitability for AAV8-mediated gene therapy.
期刊介绍:
Gene Therapy covers both the research and clinical applications of novel therapeutic techniques based on a genetic component. Over the last few decades, significant advances in technologies ranging from identifying novel genetic targets that cause disease through to clinical studies, which show therapeutic benefit, have elevated this multidisciplinary field to the forefront of modern medicine.