Scientists created "wooly mice" by editing multiple genes linked to hair growth, demonstrating advanced gene-editing capabilities crucial for bringing back mammoth-like creatures. While the focus is on the editing process itself rather than creating a mouse-mammoth hybrid, this marks a significant step toward complex genetic modifications needed for de-extinction projects.

Woolly Mice: A Gene-Editing Test Run for Mammoth Revival

The team behind the ambitious plan to resurrect mammoth-like creatures has announced the creation of "wooly mice," sporting long fur reminiscent of their extinct, giant relatives. This wasn't about creating a mini-mammoth, but a demonstration of advanced gene-editing techniques.

The creation of wooly mice showcases the team's ability to simultaneously edit multiple genes—a critical skill for introducing mammoth-like changes into the elephant genome.

Of Mice and Mammoths: Laying the Groundwork

Colossal Biosciences, spearheading de-extinction projects like the dodo and thylacine, views the mammoth project as its flagship endeavor. The strategy involves editing stem cells from closely related species (in this case, elephants) to match the genomes of their extinct counterparts.

However, working with elephants presents unique challenges:

• Long Gestation: Elephants have a 22-month gestation period, making rapid experimentation impractical.
• Ethical Concerns: Elephants are endangered with complex social structures, raising ethical questions about experimental manipulation.

Enter the humble mouse, a genetic research staple for over a century. Mice offer several advantages:

• Easy Genetic Manipulation: Researchers possess extensive tools for genetic manipulation and efficient propagation of changes to new generations.
• Visible Traits: Fur mutations in mice are easily observable, facilitating the study of gene function.

The Editorial Pipeline: Honing Gene-Editing Techniques

The team employed variations of two gene-editing approaches:

1. CRISPR/Cas9: This method creates breaks in both DNA strands at specific sequences, guided by RNA.
2. Cytosine Base Editor: This approach uses CRISPR/Cas targeting but links it to a protein that converts cytosine (C) to thymidine (T), allowing for precise mutations.

The researchers tested different guide RNAs to target specific genes, assessing the effectiveness and precision of each system in stem cells.

• CRISPR/Cas9 proved more active, editing more target genes and increasing the likelihood of editing both chromosome copies. However, it also showed a higher risk of off-target edits.
• The cytosine base editor was less active and more likely to edit only one chromosome. But, it had significantly fewer off-target effects.

Getting Woolly: The Results

Researchers targeted a variety of genes affecting mouse fur, including developmental regulators and keratin genes. Editing multiple genes—up to seven in some experiments—resulted in diverse fur phenotypes.

Mice with more gene alterations developed long, golden coats, sometimes with a shaggier appearance due to kinked hair shafts.

While a separate test of a mammoth-derived fat metabolism gene yielded no obvious changes, the real breakthrough lies in the team's ability to efficiently target multiple genes simultaneously.

Looking Ahead: Marketing Hype vs. Real Progress

Despite the hype surrounding "woolly mice," the project represents a genuine technological leap. However, significant challenges remain.

The targeted changes primarily resulted in non-functional protein versions, which are relatively easy to achieve. The mammoth project will require dozens, if not hundreds, of changes. It remains unclear whether the team can simply increase the number of genes edited simultaneously or if multiple rounds of editing will be necessary.

In conclusion, the "woolly mice" project is a blend of marketing, tangible technological progress, and unresolved challenges. It's a significant step toward the complex gene editing required for de-extinction efforts, but the path ahead remains long and complex.