Population replacement

This strategy comprises two essential steps:

Develop a modified strain of vector mosquito that is unable to transmit the pathogen of interest (or with greatly reduced ability to transmit relative to wild mosquitoes)

Introgress (i.e. spread) this ‘refractoriness gene’ or genetic system into the target population.

In many transmission settings, effective control of disease transmission by this method would require a near-ideal system, i.e. a very effective refractoriness gene, spread to a very high allele frequency, so that the overwhelming majority of mosquitoes carry at least one copy of the gene. It may be possible to reduce this requirement by combining with other approaches (drugs, vaccines, other vector control methods).

Since engineered mosquitoes are likely to have slightly reduced fitness relative to wild type mosquitoes, an engineered refractoriness gene is not expected to spread through a wild population on its own, instead natural selection is likely to lead to gradual loss of the gene, even if mosquitoes carrying it are initially released in quite high numbers.  Therefore some additional genetic system would be required to spread the refractoriness gene – a so-called ‘gene drive system’ or ‘gene driver’.  A strain intended for use in a population replacement strategy will therefore have a refractoriness gene connected to a gene drive system.

Population replacement strategies face some significant challenges.  The key attractions are:

The strategy should be relatively cheap to implement, once suitable strains have been developed and tested, as the gene system should spread itself through the target population after a relatively small initial release.

If successful, the strategy would leave the mosquito population apparently unaffected, still occupying their ecological niche, still biting people, but unable to transmit the pathogen, thereby reducing or eliminating disease transmission with minimal other effects.

The key challenges are:

Technically challenging and therefore (probably) relatively high development costs

Pathogens may develop resistance to refractory gene (likelihood can be minimised by appropriate design)

Implies permanent or long-term conversion of wild population to transgenic form

May be difficult to restrict spread of gene to target population only, unless target is entire species worldwide

May be difficult to ensure permanent linkage of gene driver and refractoriness gene (‘cargo’); without this gene driver may spread on its own without conferring the intended benefit in reduced disease transmission

Testing a self-perpetuating/self-spreading system under field conditions may be difficult, as it may tend to spread beyond the nominal trial boundaries.