| Autor: |
Smidler AL; School of Biological Sciences, Department of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA., Pai JJ; School of Biological Sciences, Department of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA., Apte RA; School of Biological Sciences, Department of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA., Sánchez C HM; Divisions of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA., Corder RM; Divisions of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA., Jeffrey Gutiérrez E; Divisions of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA.; Oxitec Ltd., Abingdon, OX14 4RQ, UK., Thakre N; School of Biological Sciences, Department of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA., Antoshechkin I; Division of Biology and Biological Engineering (BBE), California Institute of Technology, Pasadena, CA 91125, USA., Marshall JM; Divisions of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA.; Innovative Genomics Institute, University of California, Berkeley, CA 94720, USA., Akbari OS; School of Biological Sciences, Department of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA. |
| Abstrakt: |
Malaria is among the world's deadliest diseases, predominantly affecting Sub-Saharan Africa and killing over half a million people annually. Controlling the principal vector, the mosquito Anopheles gambiae , as well as other anophelines, is among the most effective methods to control disease spread. Here, we develop a genetic population suppression system termed Ifegenia (inherited female elimination by genetically encoded nucleases to interrupt alleles) in this deadly vector. In this bicomponent CRISPR-based approach, we disrupt a female-essential gene, femaleless ( fle ), demonstrating complete genetic sexing via heritable daughter gynecide. Moreover, we demonstrate that Ifegenia males remain reproductively viable and can load both fle mutations and CRISPR machinery to induce fle mutations in subsequent generations, resulting in sustained population suppression. Through modeling, we demonstrate that iterative releases of nonbiting Ifegenia males can act as an effective, confinable, controllable, and safe population suppression and elimination system. |
