Work

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

Year: 2025

Type: article

Study designs: Systematic Review, Meta-Analysis

Abstract: 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.

Source: Human Gene Therapy

DOI: 10.1089/hum.2024.221

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

Institutions: Medizinische Hochschule Hannover, Research Center for Translational Regenerative Medicine, Boston Children's Hospital, Harvard University

Language: English

Topic: Virus-based gene therapy research

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

OpenAlex ID: W4409301462

FWCI: 2.148

Cites: 34

Cited by: 4

Related to: 10