Aubrey, Gemma Kelly,
and Marco Herold
Photo courtesy of the
Walter and Eliza Hall Institute
The gene-editing technique CRISPR/Cas9 can be used to target and kill lymphoma cells with high accuracy, according to preclinical research published in Cell Reports.
Using a lentiviral CRISPR/Cas9 platform, researchers were able to kill human Burkitt lymphoma cells by locating and deleting MCL-1, a gene known to be essential for cancer cell survival.
These results suggest the technology could be used as a direct treatment for diseases arising from genetic errors.
“Our study showed that the CRISPR technology can directly kill cancer cells by targeting factors that are essential for their survival and growth,” said study author Brandon Aubrey, a PhD candidate at the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.
Aubrey and his colleagues said they engineered a lentiviral vector platform that allows for efficient cell transduction and subsequent inducible expression of small guide RNAs with concomitant constitutive expression of Cas9.
After finding they could use this system to knock out the pro-apoptotic BH3-only protein BIM in human and mouse cell lines, the team wanted to determine if it could target genes that are essential for sustained cell growth.
So they used the technique to delete MCL-1 in human Burkitt lymphoma cells. And they observed a “very high frequency” of cell killing.
The researchers also used their system to produce hematopoietic-cell-restricted TRP53-knockout mice. Along with mutations that caused loss of the TRP53 protein, the team found they had generated novel mutant TRP53 proteins that could promote lymphoma development.
“[W]e showed, for the first time, that it is possible for CRISPR technology to be used in cancer therapy,” said Marco Herold, PhD, of the Walter and Eliza Hall Institute.
“In addition to its very exciting potential for disease treatment, we have shown that it has the potential to identify novel mutations in cancer-causing genes and genes that ‘suppress’ cancer development, which will help us to identify how they initiate or accelerate the development of cancer.”
