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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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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Phages first, Borgs then. Jennifer Doudna and Jill Banfield published surprising new findings in Cell, suggesting that thousands of phages have stolen CRISPR from bacteria to deploy it against rivals. “CRISPR is so popular even viruses may use it,” Science jokes. Nature puts it seriously “CRISPR tools found in thousands of viruses could boost gene editing.”
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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.
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“Progress in science is driven by new technologies, new discoveries, new ideas – in that order” (S. Brenner). This quote by one of the greatest biologists of the 20th century came to my mind while reading a curious paper recently published in Nature. To sum up, a group from Taiwan has discovered that some cells can divide despite an absence of DNA replication.
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Nature was right in choosing CRISPR diagnostic as one of the seven technologies to watch in 2022. The latest news is a test called mCARMEN, described in Nature Medicine. Pardis Sabeti (Broad Institute/Harvard), Cameron Myhrvold (Princeton University) and colleagues adapted a massively multiplexed technology presented in 2020 to be “faster, more sensitive and more easily implemented in clinical and surveillance labs”.
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The list of the latest additions since the beginning of September is impressive. They are called CasMINI (see Molecular Cell), Cas7-11 (see Nature), OMEGAs (see Science), and come respectively from Stanford University (Stanley Qi Lab), MIT (McGovern Institute), and the Broad Institute (Zhang Lab). CasMINI is half the size of Cas9 and could be much easier to deliver. Cas7-11 is the Cas9 of RNA. OMEGAs are a new class of widespread RNA-guided enzymes, thought to be the ancestors of CRISPR.
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The Dutch town of Wageningen was already a spot on the genome-editing map for the work of the CRISPR pioneer John van der Oost. Its university now aims to inspire a worldwide change in CRISPR patents policies, by announcing that it will allow non-profit organizations to use its CRISPR technology for free for non-commercial agricultural applications.
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“Virologists have infected millions of miniature organs with SARS-CoV-2, to learn how the virus wreaks havoc and how to stop it,” writes Smriti Mallapaty in the latest issue of Nature. In one study, published in Science Immunology in 2020, researchers used CRISPR in gut organoids to identify two proteins (TMPRSS2 and TMPRSS4) that facilitate the virus entry into human cells, together with the ACE2 receptor. “Other labs are knocking out ACE2 entirely, to see whether the virus can still get in”. Here the full text of the news feature.
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”.
CRISPeR FRENZY 