RESUMEN
Population management using artificial gene drives (alleles biasing inheritance, increasing their own transmission to offspring) is becoming a realistic possibility with the development of CRISPR-Cas genetic engineering. A gene drive may, however, have to be stopped. "Antidotes" (brakes) have been suggested, but have been so far only studied in well-mixed populations. Here, we consider a reaction-diffusion system modeling the release of a gene drive (of fitness [Formula: see text]) and a brake (fitness [Formula: see text], [Formula: see text]) in a wild-type population (fitness 1). We prove that whenever the drive fitness is at most 1/2 while the brake fitness is close to 1, coextinction of the brake and the drive occurs in the long run. On the contrary, if the drive fitness is greater than 1/2, then coextinction is impossible: the drive and the brake keep spreading spatially, leaving in the invasion wake a complicated spatiotemporally heterogeneous genetic pattern. Based on numerical experiments, we argue in favor of a global coextinction conjecture provided the drive fitness is at most 1/2, irrespective of the brake fitness. The proof relies upon the study of a related predator-prey system with strong Allee effect on the prey. Our results indicate that some drives may be unstoppable and that if gene drives are ever deployed in nature, threshold drives, that only spread if introduced in high enough frequencies, should be preferred.
Asunto(s)
Tecnología de Genética Dirigida/métodos , Modelos Genéticos , Animales , Simulación por Computador , Cadena Alimentaria , Tecnología de Genética Dirigida/efectos adversos , Tecnología de Genética Dirigida/estadística & datos numéricos , Aptitud Genética , Genética de Población , Conceptos Matemáticos , Conducta Predatoria , Análisis Espacio-TemporalAsunto(s)
Tecnología de Genética Dirigida/efectos adversos , Tecnología de Genética Dirigida/legislación & jurisprudencia , Edición Génica/legislación & jurisprudencia , Medición de Riesgo , Naciones Unidas/legislación & jurisprudencia , Animales , Biodiversidad , Canadá , Congresos como Asunto , Correo Electrónico , Cooperación InternacionalAsunto(s)
Contención de Riesgos Biológicos , Tecnología de Genética Dirigida/efectos adversos , Tecnología de Genética Dirigida/métodos , Medidas de Seguridad , Animales , Derrame de Material Biológico/prevención & control , Sistemas CRISPR-Cas/genética , Culicidae/genética , Culicidae/parasitología , Drosophila melanogaster/genética , Ecosistema , Extinción Biológica , Tecnología de Genética Dirigida/legislación & jurisprudencia , Edición Génica/legislación & jurisprudencia , Malaria/parasitología , Malaria/transmisión , Ciencia Militar/métodos , Medición de Riesgo , Estados UnidosAsunto(s)
Ecología , Tecnología de Genética Dirigida , Terapia Genética/tendencias , Sistemas CRISPR-Cas , Ambiente , Tecnología de Genética Dirigida/efectos adversos , Tecnología de Genética Dirigida/métodos , Tecnología de Genética Dirigida/tendencias , Terapia Genética/métodos , Humanos , Mutagénesis Sitio-Dirigida/métodos , Mutagénesis Sitio-Dirigida/tendenciasRESUMEN
Gene drives may be capable of addressing ecological problems by altering entire populations of wild organisms, but their use has remained largely theoretical due to technical constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR nuclease Cas9 to serve as a general method for spreading altered traits through wild populations over many generations. We detail likely capabilities, discuss limitations, and provide novel precautionary strategies to control the spread of gene drives and reverse genomic changes. The ability to edit populations of sexual species would offer substantial benefits to humanity and the environment. For example, RNA-guided gene drives could potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species. However, the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application. We call for thoughtful, inclusive, and well-informed public discussions to explore the responsible use of this currently theoretical technology.
