Many wild animal species with important roles in ecosystem maintenance have been lost to extinction or are currently endangered. Small populations of endangered species are susceptible to environmental challenges due to low levels of genetic diversity and loss of alleles conferring fitness in changing environments or resistance to certain challenges.

Modern biotechnology approaches offer an avenue for genome editing of at-risk species to combat these genetic limitations and stabilize wild animal populations. Working with Revive & Restore, a nonprofit organization committed to the genetic rescue of endangered and extinct species, we are applying large-scale genome rewriting approaches to address two distinct challenges that have not yet been addressed using smaller-scale genome editing.

First, we are developing the tools and techniques for precision genome writing and engineering in domestic ferret cells as a platform for assisting conservation efforts for the endangered black-footed ferret. The only native ferret species to North America, the black-footed ferret faced near extinction as recently as the 1980’s, with wild populations thought to be extinct until a small colony was discovered in Meeteetse, Wyoming.

From this colony and the heroic efforts of the U.S. Fish and Wildlife Service, seven animals have saved the species from extinction, and are the ancestors of all ~1000 black-footed ferrets alive today.  This severe genetic bottle neck is now one of several challenges facing the species.

With the technology we are developing we aim to precisely and scarlessly replace whole genes in ferret cells, which will allow us to revive key alleles known only from museum specimens and restore natural genetic variation to the surviving population.

Second, we are using genome engineering to rewrite large genomic loci in birds, providing proof of concept for this approach by re-wilding the domestic white Leghorn chicken, a commonly used avian model species. Using approaches established in our lab, we are working to engineer genomes in chicken primordial germ cells (PGCs) by replacing known domestication loci in the white Leghorn genome with corresponding sequences from the wild red junglefowl chicken genome.

We will also identify and rewrite additional candidate loci associated with molecular, morphological, or behavioral domestic phenotypes. Ultimately, we will use this approach to generate a genome rewritten chicken exhibiting characteristics and behaviors of the wild red junglefowl. In addition to chickens, we hope to use this approach to improve genetic diversity and fitness of at-risk bird species, either by directly rewriting their genomes or by engineering birds of similar species to resemble the target species.