Colossal Biosciences, the biotech company leading efforts in de-extinction, has unveiled “woolly mice”—genetically modified rodents with long fur resembling that of a woolly mammoth. While these mice are not a fusion of mammoths and rodents, scientists achieved their distinct fur traits through the simultaneous editing of up to seven genes associated with hair growth, color, and texture.
Colossal’s approach to de-extinction involves modifying the genome of closely related living species to introduce traits of their extinct counterparts. In the case of the woolly mammoth, scientists are working with elephant stem cells to introduce key genetic adaptations. However, conducting genetic experiments on elephants presents major challenges, including a lengthy 22-month gestation period and ethical concerns surrounding the manipulation of an endangered species. To bypass these issues, the company turned to mice, which reproduce quickly and are extensively studied in genetics research. Mutations affecting their fur are also easily identifiable, making them ideal for testing genetic modifications before applying them to elephants.
To develop the woolly mice, researchers used two primary gene-editing techniques. The first was CRISPR/Cas9, a powerful tool that precisely cuts DNA at targeted locations using a guide RNA sequence. While highly effective, this method also carries the risk of off-target mutations. The second technique relied on cytosine base editing, which chemically alters DNA bases without breaking the double helix. This approach is more precise but less efficient in achieving widespread genetic changes. By introducing these gene-editing systems into mouse stem cells using electrical currents, researchers successfully modified multiple genes responsible for fur characteristics.
The results of the experiment were striking. As the number of edited genes increased, the mice developed progressively longer, shaggier fur, with some exhibiting golden coats and kinked hair shafts that contributed to a woolly texture. In a separate experiment, scientists attempted to replicate a gene variation linked to fat metabolism in mammoths, but this change did not produce any visible effects in the mice. Despite the lack of direct mammoth-related genetic changes, the study highlights advancements in multi-gene editing, a crucial step toward large-scale genomic modifications.
While the woolly mice represent a notable technical achievement, the road to mammoth de-extinction remains long and uncertain. The ultimate goal of engineering a mammoth-like elephant will require the successful editing of dozens, if not hundreds, of genes—far more than the seven tested in this study.
Additionally, most of the modifications in the mice involved disabling genes rather than introducing entirely new functional traits, a challenge that will need to be addressed in future research. Whether these techniques can be scaled up for use in elephant stem cells and embryos remains a significant hurdle.
