Researchers in the USA have developed a new RNA editing approach, which could be beneficial in treating dementia.
'Gene editing leads to changes in a genome sequence through DNA cuts, and its effects are permanent in an edited cell. While it is good at turning genes off completely, it's not great at tuning a gene's output more sensitively,' said Dr Patrick Hsu, who led the team at the Salk Institute in La Jolla, California.
The team used this fine tuning on a cellular model of frontotemporal dementia – in which a toxic protein imbalance is caused by abnormal processing of the RNA. By specifically targeting the RNA, the imbalance was reversed to near levels seen in healthy cells. The work was published in Cell.
RNA is continuously generated and broken down in the cell, so errors which can occur when unintended modifications are made are less likely to cause permanent side effects compared with genome editing.
The team are not the first to use CRISPR associated enzyme Cas13 to edit RNA (see BioNews 924) but they developed the technique by screening versions of Cas13 from different bacterial strains to find one that was most effective for use in human cells. The one that gave the best results came from Ruminococcus flavefaciens XPD3002, and the team have named it CasRx.
CasRx is a smaller molecule than Cas9 and many other types of Cas13, and is therefore easier to deliver into cells. The sheer size of the Cas9 enzyme makes it difficult to package in a viral vector, limiting therapeutic delivery options.
'Perhaps even more important is the novel method the scientists used to discover this new family of CRISPR,' said Professor Floyd Romesberg, from the Scripps Research Institute, California, who was not involved in the study.