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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Fyodor Urnov imagines CRISPR cures

Fyodor Urnov, University of California, Berkeley/Innovative Genomics Institute. Urnov is a pioneer in the field of genome editing, with a diverse background in academia, industry and the nonprofit sector. During his time at Sangamo Biosciences he co-developed and co-named human genome editing.

“Imagine CRISPR cures” is the title of the keynote by Fyodor Urnov at the World CRISPR Day conference on October 20. The talk was far from a celebration: “The fact that editing represents an approach to the majority of monogenic diseases in principle doesn’t mean that some biotech will take on disease number 823 in practice, and there are over 5,000 monogenic conditions on OMIM. Three years to IND in the best case scenario and cost scale of more than $6m per disease, that’s incompatible with either the promise of CRISPR to edit any given mutation which it can do or the unmet medical needs”. Don’t miss the on-demand video to learn more about the challenge of N=1 trials and Urnov’s call to arm against ultra-rare diseases.

Xenotransplantation: time to go deeper

Photo credit: Joe Carrotta

And so it happened. “In a first, surgeons attached a pig kidney to a human, and it worked,” as the New York Times puts it. Data are scarce, however, and all the info we have is from the general media. The kidney came from a GalSafe pig, which is the only one FDA approved so far. But scientists from several companies have already developed pigs much more engineered than that (with three or four porcine genes knocked-out instead of one, and human gene additions). To get an updated picture, we highly recommend this article published in Nature Biotechnology last April.

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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CRISPR landmark trial: who said what?

Credit Intellia Therapeutics

Here you can read a selection of notable comments about the landmark paper on in vivo genome-editing published in the New England Journal of Medicine on 26 June. The trial, conducted in the UK and New Zealand, produced the first-ever clinical data supporting the safety and efficacy of intravenous infusion of a single-dose CRISPR treatment. The treatment, developed by two US-based companies (Intellia Therapeutics and Regeneron Pharmaceuticals) targets a rare and fatal condition called transthyretin amyloidosis.

Jennifer Doudna (CRISPR co-inventor and co-founder of Intellia): “It’s a critical first step in being able to inactivate, repair, or replace any gene that causes disease, anywhere in the body” (source Science).

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GM mosquitoes play rock paper scissors

Anti-CRISPR proteins are the rock needed to stop CRISPR-based mosquito-eradicating gene drives, if necessary, and make them safer. In a news feature published last year in Nature, the molecular parasitologist Andrea Crisanti disclosed unpublished data about halting an anti-malaria gene-drive system by adding anti-drive mosquitoes to the mix. “They can completely, 100% block the drive. We can stop the [Anopheles gambiae] population from crashing,” he said. According to the scientist from the Imperial College London, it’s kind of like buying an insurance. Looking ahead to field-testing his sterilization strategy, Crisanti imagined having cages of anti-drive mosquitoes at the ready, just in case things go awry. Well, that work is now published, and anti-drive mosquitoes are a reality. To learn more, see the paper published on June 25 in Nature Communications by Chrysanthi Taxiarchi et al.

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”.