Paper of the field n°5
Click here to read more about the genome engineering with Cas9 and adeno-associated virus strategies!
Abstract for General public
Genome editing using CRISPR/Cas9 system, combined with adeno-associated virus (AAV) delivery is an efficient tool for targeted integration of a DNA template and could be used to cure multiple genetic diseases. However, scientists have discovered that this genome engineering approach may result in unexpected frequent concatemeric insertions. These concatemers are long, repeated sequences of the viral vector that integrate at the target site, potentially leading to adverse effects. Although CRISPR/Cas9 and AAV are generally effective for precise gene modifications, the study shows that these unintended concatemer formations occur in over half of edited cells and are challenging to detect with traditional PCR-based methods. The researchers establish improved detection methods to identify these insertions and suggest new strategies to reduce their occurrence by cutting the AAV vector after it enters the cell. This technology significantly decreases concatemers while maintaining the efficiency of gene editing, which is essential for ensuring safety and reliability in therapeutic applications, such as gene therapy for genetic diseases. These findings were validated in human induced Pluripotent Stem Cells (iPSCs) and Hematopoietic Stem and Progenitor cells (HSPCs).
Abstract written by Alexandra Tachtsidi from Genethon (INSERM-France)
Suchy, Fabian P., et al. « Genome Engineering with Cas9 and AAV Repair Templates Generates Frequent Concatemeric Insertions of Viral Vectors ». Nature Biotechnology, avril 2024. https://doi.org/10.1038/s41587-024-02171-w.
