A giemsa stained blood smear from a person with beta thalassemia (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)

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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Better Beer Through Gene Editing

March 27, 2018 by Kristina Panos 63 Comments

As much as today’s American beer drinker seems to like hoppy IPAs and other pale ales, it’s a shame that hops are so expensive to produce and transport. Did you know that it can take 50 pints of water to grow enough hops to produce one pint of craft beer? While hops aren’t critical to beer brewing, they do add essential oils and aromas that turn otherwise flat-tasting beer into delicious suds.

Using UC Berkley’s own simple and affordable CRISPR-CaS9 gene editing system, researchers [Charles Denby] and [Rachel Li] have edited strains of brewer’s yeast to make it taste like hops. These modified strains both ferment the beer and provide the hoppy flavor notes that beer drinkers crave. The notes come from mint and basil genes, which the researchers spliced in to yeast genes along with the CaS9 protein and promoters that help make the edit successful. It was especially challenging because brewer’s yeast has four sets of chromosomes, so they had to do everything four times. Otherwise, the yeast might reject the donor genes.

So, how does it taste? A group of employees from a nearby brewery participated in a blind taste test and agreed that the genetically modified beer tasted even hoppier than the control beer. That’s something to raise a glass to. Call and cab and drive across the break for a quick video.

Have you always wanted to brew your own beer, but don’t know where to start? If you have a sous vide cooker, you’re in luck.

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