The programmable clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) and CRISPR-Cas9-derived gene editing and manipulation tools have revolutionized biomedical research over the past few years. One important category of assisting technologies in CRISPR gene editing is methods used for detecting and quantifying indels (deletions or insertions). These indels are caused by the repair of CRISPR-Cas9-introduced DNA double-stranded breaks (DBSs), known as CRISPR's DNA cleavage footprints. In addition, CRISPR-Cas9 can also leave footprints to the DNA without introducing DSBs, known as CRISPR's DNA-binding footprints. The indel tracking methods have contributed greatly to the improvement of CRISPR-Cas9 activity and specificity. Here, we review and discuss strategies developed over that past few years to track the CRISPR's footprints, their advantages, and limitations.
Keywords: CRISPR; Cas9; DSB; Indel frequency; Indels; Off-target.