New light-controlled CRISPR tool enhances precision in genetic research
Researchers from CMM have developed BLU-VIPR, a method to control CRISPR gene-editing using light. Published in Nucleic Acids Research, this tool could greatly improve our understanding of gene functions in complex organisms.
Traditional genetic research methods at large lack necessary tools with a high level of control to modify genes in specific areas of an organism at precise times. BLU-VIPR is the newly published method that solves this by using light to target specific anatomic areas, like lymph nodes, for gene modification.
“Our new tool for light-induced CRISPR will enable researchers to understand the biological role of genes much more precisely, which in turn will increase our understanding of biological processes”, says Alexander Espinosa, CMM Team Leader, associate professor at the Department of Medicine Solna and last author of the article.
The study describes how researchers created a light-induced transcription factor, VPR-EL222, by fusing the bacterial protein EL222 with a transcription activation domain called VPR. When exposed to blue light, this factor activates guide RNA, which binds to Cas9, leading to the editing of selected genes.
Alexander Espinosa and his team first tested the effectiveness of the method in cells in vitro. Thet then went on to demonstrate it in vivo by incorporating the light-induced CRISPR system into viral vectors, successfully delivering it to primary T cells and achieving light-induced gene knockouts in T cells within the lymph nodes of mice.
The researchers will now focus on refining the system to target genes in other cells of the immune system.
BLU-VIPR represents an important advancement in genetic research, providing scientists with a highly precise tool to investigate the complex functions and roles of genes in multicellular organisms and different diseases.
Publication
“Light-induced expression of gRNA allows for optogenetic gene editing of T lymphocytes in vivo“, Pulgarin DV, Pelo N, Ferrandiz L, Tršelič T, Nyberg WA, Bowlin G, Espinosa A. Nucleic Acids Research, online 20 March 2025, doi: 10.1093/nar/gkaf213.