| dc.description.abstract | Vector-borne diseases continue to be endemic in many parts of the world with dengue, malaria, chikungunya, and yellow fever affecting millions of people every year. Recent advances in genetic engineering, such as CRISPR, have allowed for faster and cheaper DNA modification in organisms with potential to suppress the ability to transmit or carry these pathogens. Additionally, gene drive mechanisms that increase the inheritance rates of transgenic DNA have been proposed, which enable the release of very few transgenic organisms to be capable of transforming entire wild populations. The results of such actions could be irreversible with long-term consequences unknown. Methods to remove transgene DNA have been explored in crops systems and human gene therapy applications. However, such DNA self-elimination mechanisms have not yet been considered to control highly active gene drive transgenes. Here we explore the coupling of three potential gene drive mechanisms (CRISPR, MEDEA, and underdominance) and a proposed self-eliminating mechanism with system dynamics modeling.
Our results identify effective parameter spaces for the complete removal of transgenic DNA and restoration of wild-type alleles for all three gene drive mechanisms. Combining gene drive approached with a self-elimination mechanism could allow testing the effects of transgenic populations on the environment, preventing the long-term persistence of the transgene in nature. | en |
