A Crack In Creation: A Nobel Prize Winner's Insight into the Future of Genetic Engineering

by Jennifer A. Doudna

Scientists refer to this process as nonhomologous end joining, since, unlike homologous recombination, the mending does not involve a matching repair template. (Homologous derives from the Greek homologos, meaning “agreeing.”) A key property of this repair process is its inherent sloppiness. Just as a welder needs to be sure that the two pipes have clean edges before he or she joins them, the cell needs to ensure that the broken pieces of DNA have clean ends before putting them back together. Generating clean ends sometimes involves deleting or inserting a few letters of DNA, which results in permanent genetic changes after the repair process is completed. This meant that a gene would most likely be altered after being targeted by CRISPR, sliced apart, and repaired by the cell. This messy, error-prone repair would give Martin and me a simple way to detect successful gene editing. By targeting a specific gene and analyzing its DNA sequence letter by letter before and after CRISPR treatment, we would find any signs of sloppy repair, thereby proving that CRISPR had located and cut its target.