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IF 3.9 3区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Human gene therapy Pub Date : 2025-04-09 DOI:10.1089/hum.2024.221

Antonella L Bastone, Philipp John-Neek, Violetta Dziadek, Friederike Mansel, Maike Hagedorn, Jenni Fleischauer, Bettina Weigel, Gabi Paul, Axel Schambach, Michael Rothe

引用次数: 0

摘要

基因疗法中逆转录病毒载体诱导插入性肿瘤发生的潜在风险需要可靠的临床前安全性评估。在使用不同种类和设计的载体进行治疗的患者中，载体整合位点邻近基因的失调引发了造血恶性肿瘤。体外永生化（IVIM）检测法已实际应用了约 18 年，它可以量化这种诱变潜能，并在临床前阶段受到监管机构的积极要求。在此，我们对 IVIM 数据进行了全面的荟萃分析，并提供了一个循序渐进的细胞培养方案。在此基础上，我们提出将克隆生长作为诱变性的唯一指标，从成本和时间上简化了 IVIM 试验。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Meta-Analysis and Optimization of the In Vitro Immortalization Assay for Safety Assessment of Retroviral Vectors in Gene Therapy.

The underlying risk of retroviral vector-induced insertional oncogenesis in gene therapies requires a reliable preclinical safety assessment. Dysregulation of genes neighboring the vector's integration sites has triggered hematopoietic malignancies in patients treated with different vector genera and designs. With ca. 18 years in practical use, the in vitro immortalization (IVIM) assay can quantify this mutagenic potential and is actively requested by regulatory authorities during preclinical stages. Here, we present a thorough meta-analysis of IVIM data alongside a step-by-step cell culture protocol. On this basis, we propose clonal outgrowth as the single indicator of mutagenicity, simplifying the IVIM assay cost- and time-wise.

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来源期刊

Human gene therapy 医学-生物工程与应用微生物

CiteScore

6.50

自引率

4.80%

发文量

131

审稿时长

4-8 weeks

期刊介绍： Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases.