Expanding the horizons of genome editing in the fruit fly with Cas12a.

For well over a century, geneticists have relentlessly bombarded the genome of the fruit fly Drosophila melanogaster with increasingly sophisticated mutagenic agents (1). Collectively, these loss-of-function studies have been astoundingly informative, providing fundamental breakthroughs in nearly all fields of biology (2, 3). Initially, such studies relied on mutagens that attack the genome in quasirandom locations, such as X-rays, mutagenic chemicals, and transposable elements. The application of RNA interference (RNAi) to Drosophila genetics made it possible to intentionally target the transcript of any specific gene of interest and, with the Gal4-UAS system, to do so with precise spatial and temporal control (4, 5). The field was revolutionized again 7 y ago, when CRISPR-Cas9–based genome editing was demonstrated in Drosophila , making it possible to mutate and rewrite the genome of the fruit fly with ease, specificity, and scalability that were previously unimaginable (6). Yet for all of the profound properties of Cas9, the powerhouse RNA-guided DNase at the center of this technical revolution, there are downsides to relying solely on this particular nuclease for genome editing. Indeed, a growing number of alternative CRISPR approaches have been described in recent years, based on both naturally occurring and laboratory-evolved CRISPR-family proteins. To date, however, none of these alternatives have been effectively adapted for in vivo studies in Drosophila . In PNAS, Port et al. (7) provide such a demonstration, focusing on the Cas12a enzyme (formerly known as Cpf1). Cas12a displays a number of intriguing properties that make it a broadly useful complement to Cas9 (Fig. 1) and a valuable tool to continue the collective interrogation on the Drosophila genome.\n\n\n\nFig. 1. \nIn vivo genome editing with the Cas12a system offers several technical complements relative to standard Cas9-based editing in Drosophila . “NGG” and “TTTV” are the protospacer-adjacent motif (PAM) sequences required for cleavage … \n\n\n\n[↵][1]1To whom correspondence may be addressed. Email: perrimon{at}genetics.med.harvard.edu.\n\n [1]: #xref-corresp-1-1