Scholarlink

<p>Gene drive technology presents a promising approach to controlling malaria vector populations. Suppression drives are intended to disrupt essential mosquito genes whereas modification drives aim to reduce the individual vectorial capacity of mosquitoes. Here we present a highly efficient homing gene drive in the African malaria vector <i>Anopheles gambiae</i> that targets the microRNA gene mir-184 and combines suppression with modification. Homozygous gene drive (miR-184<sup>D</sup>) individuals incur significant fitness costs, including high mortality following a blood meal, that curtail their propensity for malaria transmission. We attribute this to a role of miR-184 in regulating solute transport in the mosquito gut. However, females remain fully fertile, and pure-breeding miR-184<sup>D</sup> populations suitable for large-scale releases can be reared under laboratory conditions. Cage invasion experiments show that miR-184<sup>D</sup> can spread to fixation thereby reducing population fitness, while being able to propagate a separate antimalarial effector gene at the same time. Modelling indicates that the miR-184<sup>D</sup> drive integrates aspects of population suppression and population replacement strategies into a candidate strain that should be evaluated further as a tool for malaria eradication.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月25日

查看全文
  • Sebald A. N. Verkuijl,
  • Giuseppe Del Corsano,
  • Paolo Capriotti,
  • Pei-Shi Yen,
  • Maria Grazia Inghilterra,
  • Prashanth Selvaraj,
  • Astrid Hoermann,
  • Aida Martinez-Sanchez,
  • Chiamaka Valerie Ukegbu,
  • Temesgen M. Kebede,
  • Dina Vlachou,
  • George K. Christophides,
  • Nikolai Windbichler

摘要

Gene drive technology presents a promising approach to controlling malaria vector populations. Suppression drives are intended to disrupt essential mosquito genes whereas modification drives aim to reduce the individual vectorial capacity of mosquitoes. Here we present a highly efficient homing gene drive in the African malaria vector Anopheles gambiae that targets the microRNA gene mir-184 and combines suppression with modification. Homozygous gene drive (miR-184D) individuals incur significant fitness costs, including high mortality following a blood meal, that curtail their propensity for malaria transmission. We attribute this to a role of miR-184 in regulating solute transport in the mosquito gut. However, females remain fully fertile, and pure-breeding miR-184D populations suitable for large-scale releases can be reared under laboratory conditions. Cage invasion experiments show that miR-184D can spread to fixation thereby reducing population fitness, while being able to propagate a separate antimalarial effector gene at the same time. Modelling indicates that the miR-184D drive integrates aspects of population suppression and population replacement strategies into a candidate strain that should be evaluated further as a tool for malaria eradication.