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In the process of simplifying the Circle-Seq method, we realized that our method offers much more: it can also find out if the pieces of donor DNAs (used for inserting a gene at the CRISPR cut site) are inserted correctly and if they are inserted elsewhere (random insertions).
The CRISPR-KRISPR method can also be useful for characterizing knock-in loci in other model organisms, including cell lines!
Random insertions are identified by strategically placing the guide RNAs (gRNAs) used in the CRISPR-KRISPR assay: one gRNA in one of the homology arms and the second binding to an overlapping region between the insert and the other arm. See article for more details.