Cas13 RNA editing of C9ORF72 repeat expansion for ALS and FTD

A CRISPR/Cas13 system targeting the G₄C₂ expansion in intron 1 of C9ORF72, a common cause of ALS and frontotemporal dementia, could help treat the diseases by decreasing expression of transcripts with the pathological expansion, without decreasing expression of the non-expanded isoform.

A fluorescent reporter screen in human embryonic kidney cells of 15 guide RNAs targeting C9ORF72 sites upstream of the expansion in exon1a, or flanking the expansion in intron 1, identified three guide RNAs that selectively edited their respective sites in the presence of the RNA editing enzyme RfxCas13d. ...