The latest challenge is protecting damaged tissue immediately after a heart attack with the help of base editing (see the paper published in Science by Eric Olson’s group at the University of Texas Southwestern Medical Center). But there are hundreds of devastating diseases that affect the heart or other muscles and are caused by mutations that could be fixed by CRISPR-based tools (see this paper in Science Trsnslational Medicine for example). From Duchenne dystrophy to cardiomyopathies, some preliminary results are very encouraging. Learn more reading the article on the Science paper published by El Pais and watching this video with Olson explaining his studies, especially on Duchenne muscular dystrophy.
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).
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.
Hopes are high for an experimental immunotherapy recently described in Nature, possibly the most complex treatment ever developed and tested on humans. The results of the small trial carried out by the California-based PACT Pharma look promising, even if the success is more technical and conceptual than clinical.
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.
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.
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).
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
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).
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.