Next-generation CRISPR gene-drive systems using Cas12a nuclease

Sara Sanz Juste, Emily M. Okamoto, Christina Nguyen, Xuechun Feng () and Víctor López Del Amo ()
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Sara Sanz Juste: The University of Texas MD Anderson Cancer Center
Emily M. Okamoto: University of California San Diego
Christina Nguyen: University of Texas Health Science Center, School of Public Health, Department of Epidemiology, Human Genetics, and Environmental Sciences, Center for Infectious Diseases
Xuechun Feng: University of California San Diego
Víctor López Del Amo: University of Texas Health Science Center, School of Public Health, Department of Epidemiology, Human Genetics, and Environmental Sciences, Center for Infectious Diseases

Nature Communications, 2023, vol. 14, issue 1, 1-8

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-42183-9

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