New Approach for Targeted Genome Editing in Wild Populations

Researchers from Macquarie University and the California Institute of Technology have discovered a novel method that may make it easier and more controllable for scientists to modify the genetic composition of wild populations than when using gene drives.

Using genome editing methods (e.g., CRISPR/Cas9), the method, known as an Allele Sail, introduces a range of possible genetic modifications into wild populations without the need to propagate the genome editor transgene to high frequencies.

Allele Sails offer a simple way to alter the traits and fates of wild populations, and may be more acceptable to use as the genetically modified part is introduced at low frequencies, and its persistence can be tuned.”

Michelle Johnson, Study Lead Author and Computational Biologist, California Institute of Technology

A Force for Change

Professor Maciej Maselko of Macquarie University's Applied Biosciences and Professor Bruce Hay of CalTech's Division of Biology and Biological Engineering jointly led the study.

Allele Sails operate using simple molecular mechanisms and should function efficiently in a much wider range of species than other population modification approaches, such as gene drives.”

Bruce Hay, Professor, California Institute of Technology

The basic concept is to first create transgenic organisms that express genome editors, and then use those editors to make alterations at specific, viable, and fertile locations in the genome. After being released, these organisms would procreate alongside their wild counterparts.

When kids inherit one copy of the editor and one copy of an unmodified version of the target, the editor makes the desired modification. As a result, organisms have two copies of the changed target but only one of the editors. Thus, the edit is amplified, while the editor stays at a low frequency.

In Allele Sails, the editor transgene acts like a force to push subtle modifications into a population as opposed to transgene-bearing gene-drives which act autonomously to increase their own frequency.”

Maciej Maselko, Professor, Applied Biosciences, Macquarie University

With funding from the CalTech Center for Evolutionary Sciences, the research presents findings from complex population models to investigate different Allele Sail scenarios and important parameters, such as whether either the editor or the edits are subject to negative selection or whether Allele Sails could effectively suppress pest populations by focusing on genes that would produce fewer females.

An Ocean of Possibilities

The team anticipates that Allele Sails will be used in various ways to address critical global concerns. Examples include editing coral for heat tolerance, restoring lost genetic variety crucial for disease resistance in vulnerable species, reducing mosquito pathogen transmission, reversing pesticide resistance in rodents, and making the invasive cane toad less poisonous.

These qualities can frequently be established with little modifications. In many circumstances, a single letter of nucleic acid variation is sufficient.

Johnson added, “Allele Sails could be most adept at spreading small changes that are indistinguishable from natural mutations.”

Additionally, the authors hope that by using a transgene that is present in small quantities and does not persist indefinitely, they will be able to introduce changes that are indistinguishable from those that can occur naturally, allaying public concerns and removing regulatory obstacles associated with alternative, gene-drive approaches.

“Of course, any genetic modification of wild populations will need careful study of potential environmental impacts, but Allele Sails could be an important option in situations where conventional conservation and pest management tools have not been enough on their own,” concluded Dr Maselko.