CRISPR editing of cancer gene slows cell growth

Removing the binding sites for an oncogene has been shown to slow cancer cell growth.

Researchers from the University of Helsinki, Finland have identified a mechanism by which an oncogene, a mutated gene that has the potential to cause cancer, affects cancer cell growth. The researchers identified genomic binding sites, which are a type of binding site found in DNA where other molecules may bind, and by using a variation of the CRISPR/Cas9 genome editing approach, found that removing these binding sites slowed cell growth.

'In a healthy tissue, cell growth and proliferation are tightly controlled processes. During development of cancer, cells escape these control mechanisms and grow uncontrollably,' explained Dr Päivi Pihlajamaa, senior researcher in applied tumour genomics at the University of Helsinki.

The researchers focused their studies on the MYC oncogene, which promotes the expression of genes that are important for cell growth. The MYC oncogene is overactive in over half of all human cancers, however, there are no drugs currently able to inhibit the MYC gene because its protein structure complicates therapeutic targeting.

The researchers, however, have discovered an alternative option for preventing the over activity of the MYC oncogene, by inhibiting the function of its target genes that are responsible for promoting cell growth.

The team, who published their results in Nature Biotechnology, developed a novel genome editing method to precisely measure the effects of changes in small DNA elements on cellular growth.

Previously, genome editing by CRISPR/Cas9, was able to edit with high precision and efficacy, however, it could induce DNA damage and affect cell growth. The ability to single out the effects of the mutation of interest from the ones caused by the genome editing approach itself is vital and can be achieved by the new approach, which the researchers called 'competitive precision genome editing (CGE)'.

CGE resulted in the researchers being able to assess the contribution of each specific binding site to cell growth.

'Our method... [uses] an experimental strategy in which the cells that have undergone genome editing are directly compared to each other, and the unedited wild-type cells are discarded from the analysis,' Professor Jussi Taipale, group leader of the applied tumour genomics research programme at the University of Helsinki, explained. 'The method is highly beneficial for future studies, since it can be used for investigating how various mutations affect proliferation and other cellular properties.'