Allele Sails: launching traits and fates into wild populations with Mendelian DNA sequence modifiers

Michelle L. Johnson, Bruce A. Hay, Maciej Maselko,  bioRxiv,  2024.

Population-scale genome editing can be used to alter the composition or fate of wild populations. One approach to achieving these aims utilizes a synthetic gene drive element—a multi-gene cassette—to bring about an increase in the frequency of an existing allele. However, the use of gene drives is complicated by the multiple scientific, regulatory, and social issues associated with transgene persistence and gene flow. Alternatives in which transgenes are not driven could potentially avoid some of these issues. Here we propose an approach to population scale gene editing using a system we refer to as an Allele Sail. An Allele Sail consists of a genome editor (the Wind) that introduces DNA sequence edits (the Sail) at one or more sites, resulting in progeny that are viable and fertile. The editor, such as a sequence-specific nuclease, or a prime- or base-editor, is inherited in a Mendelian fashion. Meanwhile, the edits it creates experience an arithmetic, Super-Mendelian increase in frequency. We explore this system using agent-based modeling, and identify contexts in which a single, low frequency release of an editor brings edits to a very high frequency. We also identify conditions in which manipulation of sex determination can be used to bring about population suppression. Current regulatory frameworks often distinguish between transgenics as genetically modified organisms (GMOs), and their edited non-transgenic progeny as non-GMO. In this context an Allele Sail provides a path to alter traits and fates of wild populations in ways that may be considered more acceptable.


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