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).

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.

Base-editing comes of age and more SCD news

Alexis Komor and Nicole Gaudelli developed based editing when they were postdoc in David Liu’s laboratory at Harvard. Credit: The CRISPR Journal

The first Investigational New Drug (IND) application for base-editing technology has been cleared by the Food and Drug Administration. BEAM-101, developed by Beam Therapeutics, is an ex vivo base-editing product candidate, meaning that it uses a modified form of CRISPR capable of making single base changes without double-stranded DNA cleavage.

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Meet the first CRISPR patients in Italy

Emanuele and Erika Guarini are brother and sister. They were treated for thalassemia respectively in November 2020 and August 2021 by the team of Franco Locatelli at Bambin Gesù hospital in Rome. Before the CRISPR-based treatment, they needed a blood transfusion every 15-20 days (source La Repubblica).

CRISPR patients, 3 reasons for hope

Patrick Doherty, Carlene Knight, and Victoria Gray (credit NPR)

There is one more hopeful story from NPR. It involves a woman with a congenital eye disorder who volunteered to have her retina edited. A few months ago, it was a man suffering from a rare liver disease. The first of all, as you probably know, was a woman struggling with sickle cell disease. Don’t miss their CRISPR stories!

Three August news not to be missed

by Philippa Steinberg

The Innovative Genomics Institute presents CRISPR Made Simple – the new online primer on gene editing made for kids or anyone starting from scratch.

The Broad Institute unveils SEND, a new delivery system inspired to retrotransposons (see Feng Zhang’s paper in Science)

Genotoxicity concerns: Nature Biotechnology explains how a cancer-associated phenomenon called chromothripsis could affect CRISPR therapies.

WHO’s roadmap on genome editing

A multi-disciplinary panel of 18 experts from all over the world, a two years long consultation, over 150 pages. The much-awaited report of the World Health Organization on human genome editing was delivered on July 12 and is divided into three parts: A framework for governance, Recommendations, and Position Paper. While not legally binding, it is expected to influence both governments and the scientific community, by offering a roadmap based on widely shared ethical principles and usable policy tools.

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Toward an NIH-validated CRISPR toolkit

The Somatic Cell Genome Editing (SCGE) Consortium is working to accelerate the development of better methods of editing. Seventy-two principal investigators from 38 institutions are pursuing 45 distinct but well-integrated projects, funded by the US National Institutes of Health with US$190 million over 6 years. A perspective published in Nature details their plans:

“New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled—along with validated datasets—into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit—and the knowledge generated by its applications—as a means to accelerate the clinical development of new therapies for a wide range of conditions”.