Revolutionary CRISPR Tool 'Perturb-multiome' Maps Gene Networks in Blood Cells, Offering New Hope for Treating Blood Disorders

Researchers at the Dana-Farber Cancer Institute have developed a new genomic screening tool, Perturb-multiome, to reverse-engineer genetic programming in cells. This innovative tool uses CRISPR technology to study how transcription factors influence cell growth and development, potentially revolutionizing the treatment of blood disorders. Perturb-multiome enables scientists to simultaneously knock out multiple transcription factors across different blood cell types, allowing for comprehensive analysis of gene-gene interactions. The team performed single-cell analyses to track changes in gene expression and DNA accessibility, revealing regulatory networks that govern cell differentiation and function. According to Dana-Farber Cancer Institute, variants within transcription factor-sensitive accessible chromatin regions, though representing less than 0.3% of the genome, show a ~100-fold enrichment in heritability across certain blood cell phenotypes. The research focused on immature blood cells, identifying DNA regions that significantly impact blood cell development. Many of these regions contain mutations linked to hematological disorders. This discovery may lead to new gene therapies for conditions like sickle cell disease and beta-thalassemia. The FDA has already approved some CRISPR based gene therapies for sickle cell disease. The collaborative study, involving experts from Dana-Farber and Boston Children's Cancer and Blood Disorders Center, highlights the importance of interdisciplinary approaches in addressing complex biological questions. The research was funded by organizations including La Caixa Foundation, the Rafael del Pino Foundation, and the American Society of Hematology.