Gene Technology Offers Hope for Malaria Eradication

In short, there is a hope to eradicate Malaria in the future!

There is no doubt that malaria is a disease. According to the World Health Organisation (WHO), 3.2 billion people are at risk of contracting the disease and 438 000 deaths were incurred from the 214 million cases reported in 2015 alone. Despite these alarming fatalities, improvement has been made due to various worldwide initiatives leading to 37% drop in incidence rate and 60% reduced death rate from 2000 to 2015.

This has largely been brought about by the increased active engagement of the global community and WHO in developing a robust set of guidelines for tackling the disease and facilitating coordination between countries.

Some successful policies include community education highlighting the importance of the implementation of preventative measures and wider availability of medicine. So surely we can agree that we are heading towards the right direction? Mostly yes.

The biggest challenge facing efforts in the eradication of the disease is the emergence of resistance to current therapies. The 1970s and 80s saw the widespread resistance of malaria to the antimalarial Chloroquine, resulting in widespread fatalities. Presently, the most effective treatment is artemisinin combination therapy (ACT), which earned Youyou Tu a Nobel Prize in Medicine and Physiology in 2015.

While hailed as a major stepping stone in the continuation of eradication efforts, cases of resistance are starting to emerge, mostly due to failure to follow and finish the prescription of the medicine.

This could be a major blow to WHO’s Technical Strategy for Malaria 2016–2030 which aims to eliminate the disease in at least 35 countries and reduce mortality and incidence rate to 90% worldwide. To ensure the progress of this initiative, efforts could be directed in developing new therapies and drugs, or more active preventative intervention within communities.

However, there is an unlikely yet effective alternative to the classic therapies which may make some shift uneasily in their seats: genetically modified organisms (GMO). The recent development of a genetically modified carrier mosquito of malaria made headlines due to its high potential of eliminating malaria once and for all. The malaria parasite, plasmodium, is transmitted via the mosquito anopheles and if the mosquito is unable to host the parasite, then it prevents malaria parasite transmission.

In this case, the disease vector has been the subject of the therapy rather than direct treatment in humans. This therapy is more effective as it addresses the root of transmission and will remove complications arising from clinical trials and toxicity to humans.

This technology called Gene Drive has the potential to render the mosquito unable to host the parasite or reduce the mosquito population to levels that do not support malaria transmission. In this case, the team have opted for the latter, with results showing that the mosquito populations can decrease to very low levels which nullifies transmission. This has been done by targeting three genes responsible for female fertility.

The Gene Drive system is able to remove the desired genes in each generation of mosquito offspring. This relies on the system cutting the DNA at the site of the target genes.

Then, a DNA repair mechanism fixes the broken DNA by copying from its other paired chromosome bearing the same gene (chromosome pairs are highly similar in their gene make up). However in this case, the system is able to redirect the machinery to replace the damaged gene with another constructed gene disrupting the normal gene responsible for female fertility. As a result, the offspring female will be infertile and in the long run, unable to maintain the population of the malaria carrier mosquito.[1] Of course, the challenges facing the release of such modified mosquito into the wild such as an imbalance in the ecosystem is acknowledged.

However, it is believed that by simply reducing the numbers as oppose to total annihilation of the mosquito minimises disturbance and no different to upsetting it as a result of other human activities such as hunting animals and urbanisation. As mentioned above, the objective is to merely reduce the population to levels unable to transmit the parasite.

Taking into consideration the increased levels of drug resistance and the time-consuming efforts in developing new drugs, the genetically modified mosquito has to be seriously considered by the WHO as a viable method of eradicating malaria.

[1] Hammond et al (2015) A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae, Nature Biotechnology, doi:10.1038/nbt.3439