A confinable female-lethal population suppression system in the malaria vector, Anopheles gambiae

Abstract

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jul 07, 2023
Source ID
10.1126/sciadv.ade8903

Entities

People

  • Andrea Smidler
  • Eileen Jeffrey Gutiérrez
  • Héctor Sánchez
  • Igor Antoshechkin
  • James J. Pai
  • John M Marshall
  • Neha Thakre
  • Omar S. Akbari
  • Reema A. Apte
  • Rodrigo M Corder

Organizations

  • California Institute of Technology
  • Innovative Genomics Institute
  • Oxitec
  • University of California
  • University of California, San Diego

Tags

Fields of Study

  • Biology

Readers

  • Infectious Disease/Epidemiology
  • Molecular Genetics
  • Vector-Borne Disease and Entomology

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech