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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Cholesterol down – ready set edit!

Last week Verve Therapeutics dosed the first patient with a candidate treatment for hypercholesterolemia. This is exciting news for a couple of reasons. First, the technology used: CRISPR 2.0, i.e., base-editing is hitting the clinic (see the news in Nature Reviews Drug Discovery). Second, this is a leap forward into common diseases (“CRISPR for the masses”, says The Washington Post) and a training session for the real challenge, which is to “stop the biggest killer on Earth”, cardiovascular disease (MIT Technology Review).

Hit&Run – the Italian way to epi-editing

The San Raffaele-Telethon Institute in Milan has been a leading player in gene therapy for many years. Nowadays, Angelo Lombardo, Luigi Naldini, and colleagues are making news with epigenetic editing. Their 2016 paper in Cell on hit-and-run epigenetic editing is considered seminal work. The company they co-founded, Chroma Medicine, received substantial financing, as recently reported by Nature Biotechnology. Last but not least, the presentation given in May at the annual meeting of the American Society of Gene and Cell Therapy inspired a Science news entitled “Better than CRISPR? Another way to fix gene problems may be safer and more versatile.” In brief, they injected mice to silence the expression of the PCSK9 gene, lowering “bad” cholesterol levels for months

The race of Liu’s CRISPR machines

From the base-editing idea first sketched out via email in 2013, to the invention of prime-editing in 2019. From the progeria mutation fixed in mice in 2021 to the upcoming clinical trial for coronary heart disease. The updated story of the most advanced CRISPR tools told by Harvard’s David Liu is not to be missed (here’s the link to the Life Itself conference organized by CNN).

Four tips on epigenetic editing

Credit IGI

The epigenetic way to editing is hot these days. Here are our suggested readings to keep pace:
1) the basics of the tools CRISPRoff and CRISPRon are explained on the website of the Innovative Genomics Institute
2) Nature Biotechnology news on Chroma Medicine, a company pioneering epigenetic editors
3) The Scientist on resetting the DNA of rats to reverse alcohol damage (see also the paper by Bohnsack et al. in Science Advances)
4) the review discussing translational issues in epigenetic editing published by Huerne et al. in The CRISPR Journal.

Picture of the week: Francis Collins’s bars

Francis Collins at the ASGCT 25th Annual Meeting

“Your mission is to make the red bar match the yellow bar”, urges a slide shown by Francis Collins at the annual meeting of the American Society of Gene & Cell Therapy held in Washington. There are almost 7,000 genetic diseases, but only about 500 with therapy. Most are not viable targets in a for-profit setting and won’t be managed by current gene-editing procedures. Hence the call to find something that is scalable. “We need a transformative approach.” Please read Kevin Davies’s account of the inspirational lecture given by the geneticist that led the Human Genome Project, then was appointed director of the NIH, and currently is Joe Biden’s scientific advisor.

Are you ready for CRISPR cats?

The paper “Evolutionary Biology and Gene Editing of Cat Allergen Fel d 1” is a proof of principle but this is only the first step. About 15% of humans have allergic reactions to cats and the major allergen may be nonessential for those animals, given the apparent lack of evolutionary conservation. According to the bioinformatics analysis just published by Nicole Brackett et al. from the US company InBio “Fel d 1 is both a rational and viable candidate for gene deletion, which may profoundly benefit cat allergy sufferers by removing the major allergen at the source”.

The human genome has no secrets

Twenty-one years after genome 1.0, the Telomere-to-Telomere Consortium gives us a new assembly (T2T-CHM13) generated by long-read sequencing. It adds approximately 200 megabases of accurate genetic information, roughly equivalent to a whole chromosome. As Deanna Church writes in a perspective it is “an important step to assembly models that represent all humans, which will better support personalized medicine, population genome analysis, and genome editing”. Dont’s miss this Science issue!

A promising alternative to CAR-T cells

Engineering lymphocytes to recognize cancer cells is a strategy that has already produced convincing clinical results thanks to CAR-T therapy. But this is not the only approach on the horizon. An emerging alternative is TCR-engineered lymphocytes, where TCR stands for T-cell receptors.

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