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Colossal Biosciences Says This Modern Gene Editing Tool Is Helping Bring Back the Woolly Mammoth

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Imagine miraculous innovations like curing sickle cell anemia, reviving lost species, and improving the efficiency of crop cycles. While these may seem like far-off hopes for the future, thanks to breakthroughs in gene editing and the widespread application of gene-editing tool CRISPR technology, we’re experiencing a revolution in the field of genomics and biotechnology where imagination may become the only limit to innovation.

Since the discovery of CRISPR’s limitless potential in gene editing, the tool has laid the foundation for billion-dollar companies such as Colossal Biosciences, which was founded with the goal of using CRISPR to advance the fields of conservation and medicine, respectively.

CRISPR, short for clustered regularly interspaced short palindromic repeats, are special spacer DNA sequences found in bacteria that possess the ability to search for, bind to, and cut infected DNA strands to protect themselves from a virus. A CRISPR system can identify viral DNA sequences and send a Cas (CRISPR-associated) nucleus to these sequences to make a double-stranded break in the DNA, killing the virus as it cannot repair itself.

In 2012, Jennifer Doudna, Ph.D., and Emmanuel Charpentier, Ph.D., discovered that CRISPR sequences could be manipulated into a gene-editing tool by artificially guiding a Cas nucleus throughout an entire DNA sequence to make additions and modifications (cuts) or activate gene expressions wherever desired. Doudna and Charpentier were subsequently awarded the Nobel Prize in Chemistry in 2020 for their invaluable scientific contributions.

Since this breakthrough, and the subsequent discovery that CRISPR technology could be applied to eukaryotic cells (such as plants, animals, and humans), innovations in gene editing have skyrocketed. 

Today, CRISPR technology is being used to combat everything from global climate change to food scarcity, diseases, extinction, and aging. There are countless projects around the world currently devoted to advancing the use of CRISPR. Some researchers like Harvard geneticist George Church, who helped pioneer the use of CRISPR in human cells and clinical trials, have founded entire startups dedicated to pushing the boundaries of gene editing. 

Of the multiple startups devoted to CRISPR that Church has founded is Colossal Biosciences, which he founded alongside technological entrepreneur Ben Lamm in 2021. Colossal is famous for using CRISPR technology to edit the genome of an Asian elephant in an effort to create a hybrid species with the functionality of the extinct woolly mammoth. 

When it comes to the astounding applications of CRISPR technology, bringing back the woolly mammoth is just the tip of the iceberg. As Church said on Colossal’s website, “We’ve found a way to harness CRISPR’s power for species de-extinction, however, gene editing has the potential to impact all aspects of life — from animal de-extinction and ecosystem restoration, to disease prevention and creating more sustainable human bodies.”

CRISPR Projects: Marching Toward the Future

Given that CRISPR technology can be used on nearly any organism, many researchers have set their sights on adopting the tool to combat some of humanity’s most existential threats. While any advancement in gene editing is an invaluable contribution to science, certain applications of CRISPR technology are playing a crucial role in safeguarding our future. Here are some exciting projects involving CRISPR that may play a major role in the future of life on Earth.

Disease Eradication

Since CRISPR was first discovered to work on human cells, scientists have recognized the tool’s importance in providing gene therapy to fight diseases. Some diseases, especially those caused by mutations that are monogenic (resulting from one cell), are particularly susceptible to gene therapy. These include illnesses such as sickle cell anemia and hemophilia, and a variety of cancers like leukemia, colon cancer, and melanoma. 

In recent years, there have been several instances of clinical trials of CRISPR gene therapy curing patients whose illnesses were otherwise unresponsive to treatment. Victoria Grey, who had been suffering from the debilitating pain of sickle cell anemia for 34 years, was contemplating a bone marrow transplant when, in 2019, her doctor told her about a study using CRISPR to treat sickle cell. 

Grey agreed to the treatment, and doctors removed bone marrow cells from her blood and used CRISPR to jump-start the production of fetal hemoglobin — a protein mainly produced during pregnancy. Doctors then infused more than 2 billion edited cells into Grey’s body, which, after one trial, led to fetal hemoglobin making up nearly half of the hemoglobin in her blood. This abundance of fetal hemoglobin has compensated for Grey’s defective adult hemoglobin and effectively cleared her of all symptoms of sickle cell anemia.

Grey’s story mirrors that of Alyssa, a 13-year-old girl from the U.K. whose leukemia went into remission in 2022 after receiving donor T-cells that were CRISPR-modified to seek and destroy cancer cells.

Agricultural Improvements

As a form of genetic modification, it should be no surprise that CRISPR technology has broad applications in the agricultural sector. Crop resilience is among the most beneficial uses of CRISPR. Scientists are currently using CRISPR to alter staple crops like corn, wheat, and sugarcane to withstand the changing climate and extreme conditions such as drought, intense salinity, bitter cold, and severe heat.

Researchers have also used CRISPR to improve crop resistance to pests and viruses. CRISPR can not only heighten a plant’s immune response, but can be used to insert a new immune response taken from another plant species or an entirely different organism. 

Colossal Biosciences and Using CRISPR To Fight Climate Change

Since Colossal Biosciences was co-founded by CRISPR pioneer George Church, it’s only fitting that the company dreams big in terms of gene editing innovation. While Colossal’s main goal involves using CRISPR to insert traits of the woolly mammoth into an Asian elephant, all of Colossal’s work is deeply rooted in the conservation tactics of rewilding and ecosystem restoration and further grounded by goals of curtailing climate change.

Since the extinction of the mammoth 4,000 years ago, trees (once fodder for a mammoth’s insatiable diet) have become more common in the Arctic, leading to elevated levels of warming and heat absorption and major concerns of permafrost melt, which, according to NASA has the potential to expel up to 1,700 billion tons of carbon. In reviving the woolly mammoth and rewilding the Arctic, Colossal hopes to promote an ecosystem akin to that of the mammoth’s era, a grassland rid of mostly trees with minimal heat absorption and permafrost melt.

The mammoth isn’t the only species Colossal Biosciences is bringing back to help the environment. The company plans to repopulate the island country of Mauritius with the dodo to save the island’s native plant species. While the flightless bird went extinct around 1690, nearly a third of Mauritius’ native fruits are still too large to be dispersed by other native animals, leading to most of the island’s plants being labeled as critically endangered and nearly 57% of its trees at risk of extinction.

Using CRISPR technology, Colossal is working on altering the cells of a Nicobar pigeon (the dodo’s closest living relative) to create a wild bird primordial germ cell (the precursor to sperm and eggs) with characteristics similar to the dodo. This germ cell can then be implanted in a host chicken to birth a hybrid species functionally similar to a dodo.

While Colossal’s work is nothing short of ambitious, it can only be considered a testament to the limitless potential of CRISPR technology. Few could have imagined the extent to which science and humanity would change by Doudna and Charpentier’s discovery in 2012, and even fewer know what CRISPR will have in store for us in the future. 

Colossal Biosciences’ co-founder and CEO Ben Lamm perhaps put it best when he told Texas Monthly that the CRISPR-led technological revolution is “very similar to the moon landing.”