Work

Malignancy and gene therapy in hemophilia

Year: 2025

Type: article

Abstract: Despite the misconception that adeno-associated virus (AAV) gene therapy vectors are nonintegrating, they can integrate into the host genome at a low but nonnegligible frequency, posing a theoretical risk of tumorigenesis. While AAV integration can trigger hepatocellular carcinoma in mice, no such association has been established in humans. None of the 10 cancer cases reported in AAV vector recipients so far has shown evidence that AAV integration drives tumorigenesis. However, the strength of the evidence from molecular analyses differed significantly across these cases. The scope and conclusiveness of causality assessments depended on sample quality and cross-validation using complementary analytical methods. For example, poor sample quality precluded a conclusive analysis in a case of a spinal cord tumor. Conversely, comprehensive analyses provided strong evidence that AAV integration was not the causative factor in a case of hepatocellular carcinoma. These findings underscore the need for standardization, global long-term follow-up, and careful communication of outcomes.

Source: Research and Practice in Thrombosis and Haemostasis

DOI: 10.1016/j.rpth.2025.103283

Author: Radoslaw Kaczmarek

Institutions: Indiana University Indianapolis, Indiana University School of Medicine

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: gold

Estimated APC paid: $2,250