Engineering Resistance: A CRISPR/Cas9-mediated Gene Drive for Schistosomiasis Control
Abstract/Contents
- Abstract
- Schistosomiasis is a neglected tropical disease that afflicts over 200 million people worldwide, primarily in Sub-Saharan Africa. Schistosomes are parasitic worms that infect humans, feed on blood nutrients, and may cause anemia, tissue damage, and cognitive impairments. The disease persists despite mass drug administration efforts, partially because schistosomiasis transmission depends on several environmental factors. Schistosomes spend a significant portion of their lives as parasites of aquatic snails. Targeting the snails may better control the disease. Gene drives represent one snail control method. A CRISPR/Cas9-mediated drive could engineer snails to be resistant to schistosome infection, over several host generations. This type of gene drive could prevent disease transmission to humans. However, design and implementation of a gene drive faces barriers from complex host-parasite genetics. Previous studies focused on a single gene that dictates snail resistance against schistosomiasis, but in reality, resistance depends on highly variable genetic loci. Snails use multiple genes that confer compatibility, recognition, and removal of schistosomes during infection. The thesis uses an originally designed model to monitor gene drive performance in these complex conditions. We found that neither polymorphic genetic conditions nor compatibility-based infections affected gene drive performance as much as its ability to persist within a genetically diverse population. In a multi-faceted genetic environment, with many levels of wild-type resistance, the gene drive must outcompete other genotypes in order to become fixed in a population. Field implementation of a gene drive must consider existing, wild-type resistant genotypes of resistance.
Description
| Type of resource | text |
|---|---|
| Date created | May 14, 2018 |
Creators/Contributors
| Author | Rickards, Chloe Grace |
|---|---|
| Degree granting institution | Stanford University, Department of Bioengineering |
| Primary advisor | De Leo, Giulio |
| Advisor | Wang, Bo |
Subjects
| Subject | Bioengineering |
|---|---|
| Subject | biology |
| Subject | global health |
| Subject | CRISPR |
| Subject | Cas9 |
| Subject | gene drive |
| Subject | schistosomiasis |
| Subject | modeling |
| Subject | python |
| Subject | genetics |
| Subject | gene editing |
| Subject | genetic engineering |
| Subject | disease |
| Subject | infectious disease |
| Subject | disease control |
| Genre | Thesis |
Bibliographic information
| Related Publication | Sokolow SH, Wood CL, Jones IJ, Swartz SJ, Lopez M, et al. (2016) Global Assessment of Schistosomiasis Control Over the Past Century Shows Targeting the Snail Intermediate Host Works Best. PLOS Neglected Tropical Diseases 10(7): e0004794. https://doi.org/10.1371/journal.pntd.0004794 |
|---|---|
| Related item | |
| Location | https://purl.stanford.edu/jj016vb4204 |
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Preferred citation
- Preferred Citation
- Rickards, Chloe Grace and De Leo, Giulio and Wang, Bo. (2018). Engineering Resistance: A CRISPR/Cas9-mediated Gene Drive for Schistosomiasis Control. Stanford Digital Repository. Available at: https://purl.stanford.edu/jj016vb4204
Collection
Undergraduate Theses, School of Engineering
View other items in this collection in SearchWorksContact information
- Contact
- rickards.chloe@gmail.com
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