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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Coronavirus Testing: CRISPR Technology Set To Streamline Viral Testing

May 27, 2020 by Dan Maloney 3 Comments

If we could run back 2020 to its beginning and get a do-over, chances are pretty good that we’d do a lot of things differently. There’s a ton of blame to go around on COVID-19, but it’s safe to say that one of the biggest failures of this whole episode has been the lack of cheap, quick, accurate testing for SARS-CoV-2, the virus behind the current pandemic. It’s not for lack of information; after all, Chinese scientists published the sequence of the viral genome very early in the pandemic, and researchers the world over did the same for all the information they gleaned from the virus as it rampaged around the planet.

But leveraging that information into usable diagnostics has been anything but a smooth process. Initially, the only method of detecting the virus was with reverse transcriptase-polymerase chain reaction (RT-PCR) tests, a fussy process that requires trained technicians and a well-equipped lab, takes days to weeks to return results, and can only tell if the patient has a current infection. Antibody testing has the potential for a quick and easy, no-lab-required test, but can only be used to see if a patient has had an infection at some time in the past.

What’s needed as the COVID-19 crisis continues is a test with the specificity and sensitivity of PCR combined with the rapidity and simplicity of an antibody test. That’s where a new assay, based on the latest in molecular biology methods and dubbed “STOPCovid” comes in, and it could play a major role in diagnostics now and in the future.

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Hackaday Podcast 055: The Most Cyberpunk Synthesizer, Data In Your Cells, Bubbly In Your Printer, And The Dystopian Peepshow

February 21, 2020 by Mike Szczys 2 Comments

Hackaday editors Mike Szczys and Elliot Williams discuss the many great hacks of the past week. Just in case you missed the fact that we’re living in the cyberpunk future, you can now pop off your prosthetic hand and jack directly into a synthesizer. The robot headed for Mars has a flying drone in its belly. Now they’re putting foaming agent in filament to make it light and flexible. And did you ever wonder why those pinouts were so jumbled?

Take a look at the links below if you want to follow along, and as always tell us what you think about this episode in the comments!

Take a look at the links below if you want to follow along, and as always, tell us what you think about this episode in the comments!

Direct download (60 MB or so.)

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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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