Spot the males: New gene-editing method could transform mosquito control

(Press-News.org) Researchers have developed a new “color-coded” genetic method that makes it easy to distinguish male and female mosquitoes. This innovation can help solve a major bottleneck in mosquito control strategies that rely on releasing only sterile males. The approach uses gene editing to produce dark males and pale females, offering a practical and safer alternative to current sex-separation techniques.

A new study led by Doron Zaada and Prof. Philippos Papathanos from the Department of Entomology at Hebrew University, introduces a powerful genetic approach for separating male and female mosquitoes, an essential step for large-scale mosquito control programs aimed at reducing the spread of infectious diseases such as Dengue, Zika, and Chikungunya.

Mosquito control strategies based on the mass release of males rely on the complete removal of females, which bite and transmit disease. Existing separation methods, largely based on size differences at the pupal stage, are labor-intensive, difficult to scale, and prone to letting biting females slip through. This new study presents a genetically engineered "Genetic Sexing Strain" (GSS) of the Asian tiger mosquito (Aedes albopictus) that allows sexes to be sorted automatically based on visible pigmentation.

Hijacking Sex Determination: The researchers used CRISPR gene editing to disrupt the mosquito’s yellow pigmentation gene, creating albino-like mosquitoes. They then restored normal dark pigmentation only in males by combining the yellow gene with nix, a “master switch” that converts females into fertile males. The result is a stable strain in which all males are dark and all females remain yellow, enabling fast and accurate sex separation without the need of complex equipment.

This produces an engineered sex-linked trait in mosquitoes that uses the insect's own genes," said Prof. Papathanos. “By understanding and controlling the sex determination pathway, we were able to create a system were males and females are visually different at the genetic level.”

Built-in Safety Mechanism: Beyond visual sorting, the study revealed additional advantages for field use. The researchers discovered that the yellow females lay eggs that are highly sensitive to desiccation (drying out). Unlike wild mosquito eggs, which can survive dry conditions for months, the eggs of this engineered strain die quickly if they dry out.

"This acts as a built-in genetic containment mechanism," says Doron Zaada, the study’s lead author. "Even if some females are accidentally released, their eggs won't survive in the wild, preventing any engineered strain containing our system from establishing itself in the environment."

The researchers also showed that genetically converted males closely resemble natural males in gene expression and reproductive behavior, suggesting that the technique does not compromise male fitness, an important requirement for control programs such as the Sterile Insect Technique.

"Our approach provides a versatile platform for mosquito sex separation," adds Prof. Papathanos. "By combining cutting-edge gene editing with classical genetics, we have created a scalable, safe, and efficient system. The next step is now to built on this platform and to make females different in more ways, for example in their ability to survive high temperatures or specific additives used in mosquito mass-rearing biofactories. This could finally overcome one of the biggest hurdles in genetic mosquito control."

Published in Nature Communications, the study establishes a foundation for developing next-generation mosquito control tools that are more precise, efficient, and adaptable to real-world public health needs.

END