Reaffirming the Potential of Genetics Engineering to Expand its Ripple Effects

Colossal Biosciences, the world’s first de-extinction company, has successfully raised a sum of $200M in a Series C financing.

According to certain reports, the stated round was led by TWG Global, a diversified holding company with operating businesses and investments in technology/AI, financial services, private lending, sports, and media.

Having raised more than $435M in total funding since starting out its journey in 2021, Colossal plans on using these newly-raised funds to advance its genetic engineering technologies, and at the same time, pioneer new revolutionary software, wetware, and hardware solutions. These applications, on their part, are understood to have applications beyond de-extinction, including species preservation and human healthcare.

To understand the significance of such a development, we must take into account how the path from ancient genome to living species mandates a systems model approach across computational biology, cellular engineering, genetic engineering, embryology, and animal husbandry. It also requires refinement and tuning in each step along the de-extinction pipeline to occur simultaneously.

In response, Colossal has made significant headway for ancient DNA by supporting academic labs and internal scientific research, thus aiding all core species i.e. mammoth, thylacine, and dodo. An example of the company’s progress can also be understood once you consider it has the most contiguous and complete ancient genomes to date for each of these three species.

Talk about this progress on a slightly deeper level, we begin from how Colossal’s wholly mammoth team has, thus far, generated chromosome-scale reference genomes for the African elephant, Asian elephant, and rock hyrax, all of which have been released on the National Center for Biotechnology Information database.

Next up, it has generated the first ever de novo assembled mammoth genome, and it did so using only the ancient DNA reads. Moving on, the team has further acquired and aligned 60+ ancient genomes for woolly mammoth and Columbian mammoth in collaboration with key scientific advisors. Such a comprehensive piece of data, when packaged with 30+ genomes for extant elephant species including Asian, African, and Bornean elephants, would dramatically increase the accuracy of mammoth-specific variant calling.

Alongside that, the company has derived, characterized, and biobanked 10+ primary cell lines from acquired tissue of Asian elephants, rock hyrax, and aardvark. This it has done to help company conservation and de-extinction pipelines. Another detail worth a mention is rooted in how the wholly mammoth team also became the first to derive pluripotent stem cells for Asian elephants.

Turning our attention towards Colossal’s thylacine team, it has created the highest-quality ancient genome to date for a Thylacine, at 99.9% complete. Next up, we must dig into researchers here generating ancient genomes for 11 individuals thylacines to better understand fixed variants versus population-level variation in thylacines pre-extinction.

The team has also assembled telomere-to-telomere genome sequences for all dasyurid species to provide resources for improving understanding of thylacine evolution and underpinning thylacine engineering efforts. Not just that, by improving the understanding in this area, the researchers would also be able to facilitate conservation of threatened marsupial species.

Colossal’s thylacine team also became the first to derive pluripotent stem cells in fat-tailed dunnarts, and therefore, access advanced in vitro functional workflows. The stated breakthrough also helped the company establish state of the art conservation and genomic preservation capabilities in marsupials. Apart from that, the researchers have discovered and optimized an approach to induce ovulation in a dunnart.

Then, there is the Dodo team, which has successfully conceived a complete, high coverage genome for the dodo and the critically endangered manumea (also known as the “tooth-billed pigeon” and “little dodo”). The team has even published a chromosome-scale assembly of the Nicobar pigeon (the dodo’s closest relative), while simultaneously developing a population-scale data set of Nicobar pigeon genomes for computational identification of dodo-specific traits.

Beyond that, it has created a machine learning approach to identify genes associated with craniofacial shape in birds. The idea behind that is to gene-edit targets towards resurrecting the dodo’s unique bill morphology. In case that wasn’t enough, the researchers on the Dodo team have optimized culture conditions to grow primordial germ cells (PGCs) for four bird species.

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