Fixing A Fatal Genetic Defect In Babies With A Bit Of Genetic Modification

May 27, 2025 by Maya Posch 29 Comments

Genetic defects are exceedingly common, which is not surprising considering just how many cells make up our bodies, including our reproductive cells. While most of these defects have no or only minor effects, some range from serious to fatal. One of these defects is in the CPS1 gene, with those affected facing a shortened lifespan along with intensive treatments and a liver transplant as the only real solution. This may now be changing, after the first successful genetic treatment of an infant with CPS1 deficiency.

Carbamoyl phosphate synthetase I (CPS1) is an enzyme that is crucial for breaking down the ammonia that is formed when proteins are broken down. If the body doesn’t produce enough of this enzyme in the liver, ammonia will accumulate in the blood, eventually reaching levels where it will affect primarily the nervous system. As an autosomal recessive metabolic disorder it requires both parents to be carriers, with the severity depending on the exact mutation.

In the case of the affected infant, KJ Muldoon, the CPS1 deficiency was severe with only a low-protein diet and ammonia-lowering (nitrogen scavenging) medication keeping the child alive while a search for a donor liver had begun. It is in this context that in a few months time a CRISPR-Cas9 therapy was developed that so far appears to fixing the faulty genes in the liver cells.

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Gene Editing Spiders To Produce Red Fluorescent Silk

May 21, 2025 by Maya Posch 15 Comments

Regular vs gene-edited spider silk with a fluorescent gene added. (Credit: Santiago-Rivera et al. 2025, Angewandte Chemie)

Continuing the scientific theme of adding fluorescent proteins to everything that moves, this time spiders found themselves at the pointy end of the CRISPR-Cas9 injection needle. In a study by researchers at the University of Bayreuth, common house spiders (Parasteatoda tepidariorum) had a gene inserted for a red fluorescent protein in addition to having an existing gene for eye development disabled. This was the first time that spiders have been subjected to this kind of gene-editing study, mostly due to how fiddly they are to handle as well as their genome duplication characteristics.

In the research paper in Angewandte Chemie the methods and results are detailed, with the knock-out approach of the sine oculis (C1) gene being tried first as a proof of concept. The CRISPR solution was injected into the ovaries of female spiders, whose offspring then carried the mutation. With clear deficiencies in eye development observable in this offspring, the researchers moved on to adding the red fluorescent protein gene with another CRISPR solution, which targets the major ampullate gland where the silk is produced.

Ultimately, this research serves to demonstrate that it is possible to not only study spiders in more depth these days using tools like CRISPR-Cas9, but also that it is possible to customize and study spider silk production.

An illustration of two translucent blue hands knitting a DNA double helix of yellow, green, and red base pairs from three colors of yarn. Text in white to the left of the hands reads: "Evo 2 doesn't just copy existing DNA -- it creates truly new sequences not found in nature that scientists can test for useful properties."

LLMs Coming For A DNA Sequence Near You

April 24, 2025 by Navarre Bartz 16 Comments

While tools like CRISPR have blown the field of genome hacking wide open, being able to predict what will happen when you tinker with the code underlying the living things on our planet is still tricky. Researchers at Stanford hope their new Evo 2 DNA generative AI tool can help.

Trained on a dataset of over 100,000 organisms from bacteria to humans, the system can quickly determine what mutations contribute to certain diseases and what mutations are mostly harmless. An “area we are hopeful about is using Evo 2 for designing new genetic sequences with specific functions of interest.”

To that end, the system can also generate gene sequences from a starting prompt like any other LLM as well as cross-reference the results to see if the sequence already occurs in nature to aid in predicting what the sequence might do in real life. These synthetic sequences can then be made using CRISPR or similar techniques in the lab for testing. While the prospect of building our own Moya is exciting, we do wonder what possible negative consequences could come from this technology, despite the hand-wavy mention of not training the model on viruses to “to prevent Evo 2 from being used to create new or more dangerous diseases.”

We’ve got you covered if you need to get your own biohacking space setup for DNA gels or if you want to find out more about powering living computers using electricity. If you’re more curious about other interesting uses for machine learning, how about a dolphin translator or discovering better battery materials?

A giemsa stained blood smear from a person with beta thalassemia (Credit: Dr Graham Beards, Wikimedia Commons)

Potential Cure For All Of England’s Beta Thalassemia Patients Within Reach

August 10, 2024 by Maya Posch 6 Comments

Beta thalassemia and sickle cell are two red blood cell disorders which both come with massive health implications and shortened lifespans, but at least for UK-based patients the former may soon be curable with a fairly new CRISPR-Cas9 gene therapy (Casgevy) via the UK’s National Health Service (NHS). Starting with the NHS in England, the therapy will be offered to the approximately 460 β thalassemia patients in that part of the UK at seven different NHS centers within the coming weeks.

We previously covered this therapy and the way that it might offer a one-time treatment to patients to definitely cure their blood disorder. In the case of β thalassemia this is done by turning off the defective adult hemoglobin (HbA) production and instead turning the fetal hemoglobin (HbF) production back on. After eradicating the bone marrow cells with the defective genes, the (externally CRISPR-Cas9 modified) stem cells are reintroduced as with a bone marrow transplant. Since this involves the patient’s own cells, no immune-system suppressing medication is necessary, and eventually the new cells should produce enough HbF to allow the patient to be considered cured.

So far in international trials over 90% of those treated in this manner were still symptom-free, raising the hope that this β thalassemia treatment is indeed a life-long cure.

Top image: A giemsa stained blood smear from a person with beta thalassemia. Note the lack of coloring. (Credit: Dr Graham Beards, Wikimedia Commons)

First CRISPR-Based Therapies For Sickle Cell Disease And Beta Thalassemia Approved In The UK

November 19, 2023 by Maya Posch 20 Comments

The gene-therapy-based treatment called Casgevy was recently approved in the UK, making it the first time that a treatment based on the CRISPR-Cas9 gene editing tool has been authorized for medical treatments. During the clinical trials, a number of patients were enrolled with either sickle cell disease (SCD) or β thalassemia, both of which are blood disorders that affect the production of healthy red blood cells. Of the 45 who enrolled for the SCD trial, 29 were evaluated in the initial 12-month efficacy assessment, with 28 of those found to be still free of the severe pain crises that characterizes SCD. For the β thalassemia trial, 42 patients were evaluated and 39 were still free of the need for red blood cell transfusions and iron chelation after the 12-month period, with the remaining three showing a marked reduction in the need for these.

Both of these blood disorders are inherited via recessive genes, meaning that in the case of SCD two abnormal copies of the β-globin (HBB) gene are required to trigger the disorder. For β thalassemia a person can be a carrier or have a variety of symptoms based on the nature of the two sets of mutated genes that involve the production of HbA (adult hemoglobin), with the severest form (β thalassemia major) requiring the patient to undergo regular transfusions. Both types of conditions have severe repercussions on overall health and longevity, with few individuals living to the age of 60.

The way that the Casgevy treatment works involves taking stem cells out of the bone marrow of the patient, after which the CRISPR-Cas9 tool is used to target the BCL11A gene and cut it out completely. This particular gene is instrumental in the switch from fetal γ globin (HBG1, HBG2) to adult β globin form. Effectively this modification causes the resulting cells to produce fetal-type hemoglobin (HbF) instead of adult HbA which would have the mutations involved in the blood disorder.

For the final step in the treatment, the modified stem cells have to be inserted back into the patient’s bone marrow, which requires another treatment to make the bone marrow susceptible to hosting the new cells. After this the patient will ideally be cured, as the stem cells produce new, HbF-producing cells that go on to create healthy hemoglobin. Although safety and costs (~US$2M per patient) considerations of such a CRISPR-Cas9 gene therapy may give pause, this has to be put against the prospect of 40-60 years of intensive symptom management.

Currently, the US FDA as well as the EU’s EMA are also looking at possibly approving the treatment, which might open the gates for similar gene-therapies.

Top image: A giemsa stained blood smear from a person with beta thalassemia. Note the lack of coloring. (Credit: Dr Graham Beards, Wikimedia Commons)

Hacking The Wooly Mammoth

September 14, 2021 by Al Williams 19 Comments

In case you can’t get enough Jurassic Park movies, you can look forward to plans a biotech company has to hybridize endangered Asian elephants with long-extinct wooly mammoths using gene splicing and other exotic techniques.

Expect a long movie, the team hopes to have calves after six years and we don’t think a theme park is in the making. The claim is that mammoth traits will help the elephants reclaim the tundra, but we can’t help but think it is just an excuse to reanimate an extinct animal. If you read popular press reports, there is some question if the ecological mission claimed by the company is realistic. However, we can’t deny it would be cool to bring an animal back from extinction — sort of.

We aren’t DNA wizards, so we only partially understand what’s being proposed. Apparently, skin cells from a modern elephant will serve as a base to accept extracted mammoth DNA. This might seem far-fetched but turns out the mammoth lived much more recently than we usually think. When they die in their natural deep-freeze environment, they are often well preserved.

Once the gene splicing is set up, a surrogate elephant will carry the embryo to term. The hope is that the improved breed would be able to further interbreed with natural species, although with the gestation and maturity times of elephants, this will be a very long time to bear fruit.

So how do you feel about it? Will we face a movie-level disaster? Will we get some lab curiosity creatures? Will it save the tundra? Let us know what you think in the comments.

DNA manipulation has gone from moon-shot-level tech to readily accessible in a very short amount of time. In particular, CRISPR, changes everything and is both exciting and scary on what it puts in the hands of nearly anyone.

Emmanuelle Charpentier And Jennifer Doudna Sharpened Mother Nature’s Genetic Scissors And Won The Nobel For It

November 3, 2020 by Kristina Panos 8 Comments

It sounds like science fiction — and until 2012, the ability to cheaply and easily edit strings of DNA was exactly that. But as it turns out, CRISPR/Cas9 gene editing is a completely natural function in which bacteria catalogs its interactions with viruses by taking a snippet of the virus’ genetic material and filing it away for later.

Now, two women have won the 2020 Nobel Prize in Chemistry “for developing a method for genome editing”. Emmanuelle Charpentier and Jennifer Doudna leveraged CRISPR into a pair of genetic scissors and showed how sharp they are by proving that they can edit any string of DNA this way. Since Emmanuelle and Jennifer published their 2012 paper on CRISPR/Cas9, researchers have used these genetic scissors to create drought-resistant plants and look for new gene-based cancer therapies. Researchers are also hoping to use CRISPR/Cas9 to cure inherited diseases like Huntington’s and sickle cell anemia.

The discovery started with Emmanuelle Charpentier’s investigation of the Streptococcus pyogenes bacterium. She was trying to understand how its genes are regulated and was hoping to make an antibiotic. Once she teamed up with Jennifer Doudna, they found a scientific breakthrough instead.

Dr. Emmanuelle Charpentier via Wikimedia Commons

Emmanuelle Charpentier Fights Flesh-Eating Bacteria

Emmanuelle Charpentier was born December 11th, 1968 in Juvisy-sur-Orge, France. She studied biochemistry, microbiology, and genetics at the Pierre and Marie Curie University, which is now known as Sorbonne University. Then she received a research doctorate from Institut Pasteur and worked as a university teaching assistant and research scientist. Dr. Charpentier is currently a director at the Max Planck Institute for Infection Biology in Berlin, and in 2018, she founded an independent research unit.

Upon completion of her doctorate, Dr. Charpentier spent a few years working in the States before winding up at the University of Vienna where she started a research group. Her focus was still on the bacteria Streptococcus pyogenes, which causes millions of people to suffer through infections like tonsillitis and impetigo each year. It also causes sepsis, which officially makes it a flesh-eating bacterium.

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