Eliminating Schistosomiasis with Gene Drive – DriveOutSchisto

Schistosomiasis, an incapacitating parasitic disease, remains a major global health concern, with approximately 250 million individuals in need of treatment. It is highly prevalent in sub-Saharan Africa, South America, and Southeast Asia. Despite extensive control measures—including mass drug administration in endemic regions and the application of molluscicides to water bodies to eliminate the intermediate snail host—complete eradication by 2030, as advocated by the World Health Organization, appears unlikely under current strategies. Furthermore, the recent emergence of endemic schistosomiasis in Corsica raises concern about its potential further spread to continental areas in Europe.
In response, this project explores the application of gene drive technology, a CRISPR-Cas-based genetic engineering method that promotes the inheritance of targeted genes beyond classical Mendelian frequencies. Schistosome sex determination is based on W and Z chromosomes, wherein female sex is determined by the W chromosome. The proposed strategy exploits this genetic mechanism by selectively disrupting female-specific repetitive sequences on the W chromosome (“W-shredder”), effectively skewing the population sex ratio toward males, and ultimately driving parasite eradication. A major challenge in introducing transgenes is that they can be silenced when they integrate into regions of the genome subject to heterochromatin formation. To overcome this, our approach goes beyond use of standard genetic annotation by additionally mapping the Schistosoma mansoni chromatin landscape. By combining sequence-based annotations with chromatin structure data, we identify "genomic safe harbors” (GSH) that allow for gene insertion without interrupting essential functions, minimize off-target effects, and that are in regions of open, transcriptionally permissive chromatin.
Given the transformative scope of gene drive approaches, profound ethical and philosophical questions must be addressed. On one hand, there is a moral imperative to alleviate the disease burden experienced by millions; on the other, deliberate intervention at the genetic level to remove an entire parasite species poses significant ethical dilemma. Accordingly, the project will integrate philosophical inquiry, as well as community engagement with representatives from an endemic area in Brazil, to ensure that a broad spectrum of perspectives is considered.
We believe that the uniqueness of our project rests on four key elements. First, a continuous philosophical framework will guide project development, ensuring that technical achievements are aligned with considered moral principles. Second, mathematical modeling will be employed from the outset to integrate biological and sociological data, thereby informing and refining experimental approaches. Third, the project specifically targets the parasite rather than its intermediate snail vector, which exhibits low infection rates under natural conditions, thereby minimizing potential ecological disruption and maximising benefit for the communities. Finally, advanced genetic and epigenetic methods will be used to identify and use GSH for insertion of the gene drive constructs into the schistosome sex chromosomes.
Alongside scientific publications, the consortium will prepare green paper–style documents aimed at informing health authorities, enabling evidence-based decision-making for the control and potential eradication of schistosomiasis. We will also produce outreach videos and social media “shorts” in Portuguese, French, and English to engage broader communities and stakeholders.
We hope that this comprehensive effort—merging scientific, ethical, and sociological expertise—has the potential to complete current control strategies and significantly reduce the global burden of schistosomiasis, but can also inform similar strategies against other snail-borne diseases and beyond.