Malaria: Scientists urged to not underestimate CRISPR’s dangers

Chan
Posted: 04/23/2018

Similar to new Hollywood feature Rampage, a recent study has urged the life sciences industry not to underestimate the dangers that could hide within CRISPR Cas9.

dna

Although the film has been criticised for wildly exaggerating the capabilities of the gene editing technique, it can be recognised for its effort to draw focus from the excitable buzz around CRISPR Cas9 towards the importance of considering the ethics and dangers associated with the tool.

A recent commentary piece also emphasised the importance of methodically debating the potential outcomes of CRISPR within the task of tackling Malaria.

Malaria is spread by the bite of female mosquitos holding the Plasmodium parasite. Plasmodium falciparum causes life threatening malaria.

Progress made so far

In the five years to 2015, 17 countries managed to eradicate malaria –including the likes of Senegal and Bolivia. In this period, mortality fell by 50% and incidences fell by 15% – preventing over 6 million deaths.

The World Health Organisation (WHO) recently launched “the world’s first malaria vaccine that has been shown to provide partial protection against malaria in young children.”  After establishing efficacy in Phase 3 clinical trials a vaccine implementation programme is due to commence within this year’s immunization projects in Ghana, Kenya and Malawi.

A long way to go

Government spend on malaria prevention has seen a dramatic increase over the past decade. Although, experts note that around $6.5 billion of funding by 2020 will be key to hitting the WHO’s 2030 goal to wipe out malaria in 35 countries and shrink incidents and deaths by 90%.

Statistics claim that malaria still kills one child every two minutes.

Sub-Saharan Africa, as noted by Tanvi Nagpal, housed around 80% of the world’s malaria cases in 2016. “Their high infection rates are compounded by insufficient domestic budgets and struggling health systems.”Reports recently emerged stating of one in four blood banks in certain areas of Sub-Saharan Africa host supplies infected with malaria causing parasites.

What is CRISPR Cas9?

Researchers are now turning to CRISPR Cas9 to stop the disease at the source of transmission – the mosquito. 

The genome-editing system based on CRISPR-Cas9 is becoming a valuable tool for different applications in biomedical research, drug discovery and human gene therapy by gene repair and gene disruption, gene disruption of viral sequences and programmable RNA targeting.  The tool permanently manipulates gene expression by using programmable DNA nuclease and can remove faulty genes from a DNA sequence.

Human Genetics Scientist, Joyce El Hokayem notes that in comparison to other gene editing techniques like TALENS and zinc finger nucleases or gene transfer approaches, not only is CRISPR Cas9 cheaper but also much simpler to design because the process only requires making a short RNA sequence.

These are just some of the benefits exciting the industry. It provides discovery labs with a path to quicker generations of diseases for target identification and autologous cell therapies. Mosquitoes could, theoretically, be engineered to not transmit diseases like malaria and dengue fever. Scientists could even dampen the mosquitoes’ female fertility gene.

Ethical considerations and dangers

However, the application of CRISPR may take decades to perfect to prevent detrimental and unpredicted consequences to individuals, ecosystems and society as a whole.

In their commentary piece Maria Patrão Neves of the University of the Azores and Christiane Druml - a UNESCO Chair on Bioethics of the Medical University of Vienna, asks could any harmful effects be caused to humans bitten by an edited mosquito? Also, do humans have an inherent right to edit other biological species?

There are a few obvious areas for improvement with CRISPR– precision and efficiency being two key aspects.

In regards to the efficiency needed for a therapeutic context, Dr Andrew Bassett Postdoctoral Fellow Genome Engineering Oxford said that development is needed. “Just, for example, the off target effects. If you’re targeting in a dish with a few million cells, it’s not so dramatic. But if you’re targeting in the whole of the human body…you need to have an incredibly low off target rate in order for that to be relevant.”

Recently specialists have been deploying innovative technologies, such as predictive software to guide RNAs, that allow scientists to overcome these drawbacks.

In any case, the study’s authors maintained the genome techniques should only be applied in a therapeutic context when side effects are adequately known with the support of working groups and guidelines.

“The decision to use CRISPR/Cas9 to fight malaria, or genome editing in general, does not belong solely to science, but also requires public engagement, especially from the African communities living in malaria-endemic areas. These communities suffer from chronic poverty and are particularly vulnerable to foreign economic interests, and having low levels of education, they lack the capacity for informed debate and free decision-making.”

Despite these challenges, considering the permanent moderations CRISPR Cas9 can make to life itself the communities being impacted first should be given an influential say in this debate.

Originally published at Imperial College London Institute of Global Health Innovation.

Chan
Posted: 04/23/2018

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