CRISPR from bench to bedside

The progress of the new therapies of the CRISPR era can be told by interweaving two stories. The first is the one featuring Victoria, Carlene, Patrick, Alyssa, Terry and many others. There are over two hundred patients who have so far undergone some experimental treatment based on genome editing, i.e. the targeted correction of DNA instead of the addition of extra genes as in classical gene therapy. These women and men suffering from serious diseases had to face increasing pain and sacrifice until they decided to pin their hopes on a new type of experimental therapy, which is promising but not without risks. For the unluckiest of them, this act of courage and faith in science was not enough, but for many of these pioneers, life really did change. In fact, there are already dozens of people who have managed to free themselves (hopefully in the long term) from the burden of a rare genetic disease or, in some cases, leukaemia. Along with genetically edited cells, a new normalcy has arrived for them and the chance to finally think about the future.

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Duchenne: a farewell and some timid hope

The death of pioneer patient Terry Horgan is a warning about the risks of viral vectors but the focus is now on the first gene therapy being approved in the US

On the chellenging frontier of advanced therapies, every death is a pain from which everything possible must be learned. The inauspicious outcome of the individual treatment for Duchenne muscular dystrophy developed by the non-profit Cure Rare Disease for Terry Horgan, and tested solely on this American boy, can teach little about the specifics of CRISPR. Indeed, the death occurred before the molecular editing machine could get into action. But the information on the case, circulated in May on a preprint archive awaiting peer-reviewed, is nonetheless a valuable contribution to the advancement of knowledge in an area where science has no intention of giving up.

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Check out the pangenome, the graph of us all

The new pangenome reference is a collection of different genomes from which to compare an individual genome sequence. Like a map of the subway system, the pangenome graph has many possible routes for a sequence to take, represented by the different colors. Credit: Darryl Leja, NHGRI

We used to imagine DNA as the book of life, the code, the Rosetta stone of Homo sapiens. But the repertoire of metaphors needs updating. Today, our species portrait has taken on the appearance of a network of nodes and relationships. Welcome to the age of the pangenome: the collective genome (pan in Greek means everything) that aspires to become more and more complex, plural, cosmopolitan and inclusive.

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The lesson of Terry, the pioneer patient who didn’t make it

Terry and Richard Horgan (Courtesy of Cure Rare Disease)

He was the first patient to get a CRISPR therapy for muscular dystrophy. The first to receive a CRISPR treatment made specifically for him. And also the first to try a CRISPR approach that did not aim to change a DNA sequence but only its expression (epigenetic editing). Six months after Terry Horgan’s passing, his brother Richard disclosed the first information on the cause of death.

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Chronicles from the London editing summit

CRISPR patient Victoria Gray talking at the summit (credit The Royal Society)

The third – and perhaps final – act of the Human Genome Editing Initiative ended last week. The first summit (Washington 2015) was held amid enthusiasm for the invention of CRISPR, with the aim of fostering a constructive dialogue between science and society. The second edition (Hong Kong 2018) was dominated by the birth in China of the first edited human beings. The main points in the agenda of geneticists and bioethicists meeting a few days ago (London 2023) was to overcome the shock and focus on the next challenges: broadening the range of treatable diseases, reducing the costs of therapies, simplifying them so they can be administered anywhere in the world, and reach as many sick people as possible.

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CRISPR good and bad news as 2023 starts

Nature suggests a number of science events to watch for in the new year. Among the developments set to shape biomedical research in 2023 we will hopefully welcome next-generation mRNA-based vaccines, the updated list of WHO priority pathogens and promising candidate drugs for Alzheimer’s. Gene editing is also not missing, with the the first approval of a CRISPR-based therapy a mere 10 years after the Doudna-Charpentier invention (more about exa-cel here).

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CRISPR biofortified foods

Nutritional improvement of crops is one of the fields set to gain from the advent of genome editing. Let’s take vitamin D3. People suffering from its deficiency in the world number about one billion. Plants do not contain it naturally, but some of them (solanaceae) are able to produce its precursor (cholesterol) within a biosynthetic pathway that leads to the synthesis of certain secondary metabolites (glycoalkaloids). Luckily, they can be induced to accumulate provitamin D3 by switching off the gene responsible for this reaction.

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Exa-cel, the first CRISPR therapy moves closer to market

Rodger Novak is the president of CRISPR Therapeutics, a company he co-founded with Emmanuelle Charpentier in 2013. Jennifer Doudna was invited to join but declined.

The road from clinical trials to regulatory green light now appears to be downhill for the treatment for sickle cell anemia developed by CRISPR Therapeutics, the company co-founded by Emmanuelle Charpentier. We knew it as CTX001 but it has changed its name to exa-cel (which stands for exagamglogene autotemcel). It was one of the first CRISPR-based gene therapies to enter clinical trials, in 2019. It changed the lives of Victoria Gray and dozens of sickle cell anemia and thalassemia patients enrolled in several countries. Now it also leads the way in the late stage of the regulatory process, both in Europe and the United States, and could come to market first, in 2023. For more information see the press-release by Vertex, that collaborates at exa-cel manufacturing, regulatory and commercialization.

Give gene therapy a market chance

From Jakob Kamil Guziak’s website

The scientific renaissance is still there, but the commercial abandonnement is already going on. Patients affected by rare diseases and their families are worried they won’t be able to get treatments that are safe and effective but unprofitable for drugmakers. Take a look at the story of Jakob Kamil Guziak, recently told by Business Insider.

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