ETH Researchers Combine Base Editing and Prime Editing in Genetic Variant Scanning

Researchers at ETH Zurich in Basel have made significant strides in understanding how mutations in a cell's genome impact its function. By utilizing CRISPR-Cas technology, they have devised a new method to assess the contribution of gene variants to cancer development by generating numerous cells with different gene variants.

Published in Nature Biotechnology and led by ETH professor Randall Platt, PhD, the study involved modifying the EGFR gene in over 50,000 different ways across human cell lines. This allowed the team to investigate cancer-relevant regions within the gene, shedding light on mutations that can lead to cancer or influence drug resistance.

Combining cytosine and adenine base editors with prime editing, researchers were able to create diverse variants of the EGFR gene systematically. This approach unveiled novel insights into EGFR activation and sensitivity to tyrosine kinase inhibitors, presenting potential implications for future clinical decision-making.

Moreover, their findings highlighted previously unknown genetic variants associated with cancer and identified a potential mechanism through which EGFR mutations trigger tumorigenesis. This sophisticated framework provided depth in analyzing genetic elements, offering a high-resolution view to interpret the significance of various gene variants in a clinical context.

Overall, the use of this multimodal precision editing strategy could revolutionize genetic variant scanning, potentially enabling a more comprehensive understanding of genetic diversity and its impact on disease progression and treatment outcomes. Through meticulous testing and analysis of thousands of variants, the researchers at ETH Zurich have laid a strong foundation for further exploration and advancements in precision medicine and genetic research.