Next-generation CRISPR gene-drive systems using Cas12a nuclease

• Published in: Nature communications Vol. 14; no. 1; p. 6388
• Main Authors: Sanz Juste, Sara, Okamoto, Emily M., Nguyen, Christina, Feng, Xuechun, López Del Amo, Víctor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12-10-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 42; 42/44; 42/70; 631/208/4041; 631/208/4041/3196; 631/61/338/552; 64; 64/24; Active control; CRISPR; Directional control; Disease control; Humanities and Social Sciences; Infectious diseases; Insects; multidisciplinary; Nuclease; Pests; Populations; Science; Science (multidisciplinary); Temperature dependence; Vector-borne diseases; Vectors; Vectors (Biology)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-42183-9

One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of alternative gene drive arrangements. Yet, other nucleases such as the temperature sensitive Cas12a have not been explored for gene drive designs in insects. To address this, we herein present a proof-of-concept gene-drive system driven by Cas12a that can be regulated via temperature modulation. Furthermore, we combined Cas9 and Cas12a to build double gene drives capable of simultaneously spreading two independent engineered alleles. The development of Cas12a-mediated gene drives provides an innovative option for designing next-generation vector control strategies to combat disease vectors and agricultural pests.
One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. Here the authors describe a Cas12a gene drive system whose activity can be finetuned in a temperature-dependent manner.