Colossal Biosciences creates the Colossal Woolly Mouse
A breakthrough in genome engineering
Colossal Biosciences has announced a significant breakthrough in genetic engineering by creating the Colossal Woolly Mouse, a living organism engineered to express multiple mammoth-like traits. This provides a substantial step toward the revival of the woolly mammoth.
By successfully modifying the genomes of mice to reflect traits relevant to cold adaptation, US-based Colossal has demonstrated the feasibility of engineering complex genetic combinations that could eventually lead to the de-extinction of the mammoth.
This achievement results from advanced multiplex genome editing, where seven genes were simultaneously modified to express traits associated with the woolly mammoth, including coat colour, texture, and thickness—features vital for surviving in cold climates.
Creating these genetically altered mice is the first tangible demonstration of the company’s potential to use genetic engineering to recreate the woolly mammoth’s defining characteristics.
Ben Lamm, Co-Founder and CEO of Colossal Biosciences, described the creation of the Colossal Woolly Mouse as a monumental milestone in the company’s de-extinction mission.
“By engineering multiple cold-tolerant traits from mammoth evolutionary pathways into a living model species, we’ve proven our ability to recreate genetic combinations that nature took millions of years to evolve. This success brings us closer to bringing back the woolly mammoth,” he said.
Colossal’s mammoth team studied a dataset of 121 mammoth and elephant genomes, including high-quality reference genomes of both Asian and African elephants, to identify genes that influence cold-adaptation traits like hair texture, colour, and lipid metabolism.
Focusing on genes with fixed differences between mammoths and their closest relatives, Asian elephants, the team narrowed their research to ten genes related to hair growth, thickness, texture, and other key factors like lipid metabolism, that were compatible for expression in mice.
Using a combination of three gene-editing technologies—RNP-mediated knockout, multiplex precision genome editing, and precision homology-directed repair (HDR)—the team edited the genomes of mice to modify seven specific genes. Remarkably, some edits achieved near-perfect efficiencies, with some reaching as high as 100%.
The resulting Colossal Woolly Mice exhibit numerous traits reminiscent of the woolly mammoth. For example, by editing the FGF5 gene, which regulates hair growth cycles, the team enabled the mice to grow hair up to three times longer than wild-type mice.
Similarly, alterations to the FAM83G, FZD6, and TGM3 genes resulted in the woolly mice developing hair with a wavy, woolly texture and even curled whiskers—traits akin to the mammoth’s distinctive fur.
The Colossal Woolly Mouse expresses other features besides hair texture and growth. The team introduced a modified version of the MC1R gene, responsible for melanin production, to produce golden hair rather than the typical black or agouti coat of wild-type mice.
They also engineered a truncated version of FABP2, a lipid metabolism gene that mirrors a similar change in mammoths. This modification led to changes in the mice’s body weight, further mimicking the mammoth’s adaptation to cold climates.
The colossal woolly mouse also carries a non-functional version of the TGFA gene and a mutation in the KRT27 gene, which have been linked to the woolly mammoth’s thick coat. These alterations contribute to the wavy coat seen in the colossal woolly mice, making them one of the most complex genetically engineered animals ever created.
The Colossal Woolly Mouse is a proof of concept for mammoth de-extinction and a model organism for studying how multiple genes interact to produce complex traits. It is the first living animal engineered to express various cold-adapted characteristics, and it opens up new avenues for researching how such adaptations could be applied to other species.
Future studies will explore how these genes work together and how they can be further refined to achieve even more accurate mammoth representations.
Dr. Beth Shapiro, Chief Science Officer at Colossal, highlighted the breakthrough’s importance, saying, “The Colossal Woolly Mouse showcases our ability to use the latest genome editing tools to drive predictable phenotypes. This is an important step toward resurrecting traits lost to extinction and restoring them to life.”
Dr. Michael Abrams, co-leader of the Mammoth Team at Colossal, also expressed pride in the achievement. “We’ve pushed the boundaries of genetic engineering by coordinating multiple complex trait modifications in living animals with exceptional efficiency. This accomplishment demonstrates our scientific expertise and the power of our platform to deliver predictable phenotypic outcomes.”
The implications of the Colossal Woolly Mouse extend far beyond the laboratory. This success highlights the potential for using multiplex gene editing to de-extinct the woolly mammoth and other extinct species, opening up ecosystem restoration and species repopulation possibilities.
George Church, Professor of Genetics at Harvard Medical School and co-founder of Colossal, also commented on the breakthrough: “The Colossal Woolly Mouse demonstrates the progress we’ve made in precise genome engineering, with profound implications for multi-gene de-extinction and engineering.”
As Colossal continues to refine its approach, the Colossal Woolly Mouse stands as a key milestone in the race to bring back the woolly mammoth—and possibly even more—through the power of genetic engineering.
Colossal Biosciences is a leader in applying CRISPR technology for species de-extinction, conservation, and ecosystem restoration. Founded by Ben Lamm and George Church, Ph.D., Colossal aims to leverage cutting-edge science and technology to bring extinct species back to life and protect endangered species for future generations.
Image: The Colossal Woolly Mice exhibit numerous traits reminiscent of the woolly mammoth. Credit: Colossal Biosciences
