Gene Editing: Not Just CRISPR

Angelo De Palma

…… Zinc finger nuclease (ZFN) led the surge chronologically, followed by TALEN, then CRISPR. Each succeeding development eclipsed the previous one by virtue of easier use and greater familiarity with gene editing. CRISPR is generally credited with being significantly easier to use, hence its wide adoption among basic researchers.

Yet despite sales of ZFN reagents tailing off to baseline, and TALEN use dropping nearly as precipitously, those methods still hold promise for what is arguably the most value-driven gene editing application of all—therapy. ZFN and TALEN have reputations for being more precise than CRISPR. A recent paper by Schaefer et al., in Nature Methods that described deep sequencing to uncover off-target CRISPR effects, reinforced this belief. The authors noted that “concerns persist regarding secondary mutations in regions not targeted by the single guide RNA…We found an unexpected number of single-nucleotide variants…compared with the widely accepted assumption that CRISPR causes mostly indels at regions homologous to the sgRNA.”

ZFN and TALEN have reputations for being more precise than CRISPR.

“The simplicity and accessibility of CRISPR to researchers has democratized genome editing and changed the face of disease research to the benefit of scientists and, in fact, the world,” says Martha S. Rook, Ph.D., head of gene editing and novel modalities at MilliporeSigma. “However, mature gene-editing technologies such as ZFN and TALEN remain the methods of choice for critical research where clear intellectual property rights are desirable.”

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