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。

IF 4.5 3区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Alexander Kozikowski, Qing Wang, Cheng Yang, Neil Gordon, Kristina M Ciociola, Asanka Yapa, Claudia Villa, Paul Lambotte, Thomas Pisani, Javan Esfandiari, Angelo H Gunasekera
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引用次数: 0

摘要

先前存在的抗AAV抗体对腺相关病毒(AAV)介导的基因治疗的成功构成了重大挑战,因为它们会降低治疗效果,限制患者的治疗资格,并在治疗期间引起严重的健康问题。本研究引入了首个即时检测(POC)技术,利用Chembio的双路径平台(DPP)技术,快速定量检测患者血浆、血清和血液中的AAV8结合抗体。DPP AAV8总抗体(TAb)检测在样品添加后20分钟内提供结果,当使用纯化的与AAV8结合的人多克隆抗体进行评估时,动态范围为0-32µg/ml,相对于Chembio的AAV8 TAb ELISA具有合理的特异性和敏感性(R²= 0.90)。此外,该检测与Chembio的AAV8中和抗体(NAb) ELISA和基于细胞的NAb检测具有很强的相关性(血浆中R²= 0.97)(基于细胞的检测改编自BioAgilytix欧盟协议)。这种快速可靠的检测方法有助于筛选潜在的基因治疗患者是否存在与AAV8结合的抗体,并评估其是否适合AAV8介导的基因治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Gene Therapy
Gene Therapy 医学-生化与分子生物学
CiteScore
9.70
自引率
2.00%
发文量
67
审稿时长
4-8 weeks
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.
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