Ode to Darwin, from Phages to Borgs

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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Illuminating the Dark Genome

The December issue of Le Scienze (the Italian edition of Scientific American) has a feature by me on the ignorome. Yes, you read that right: the ignorome is the genome of which we ignore all or most, and it amounts to about a third of the total. The so called “dark genes” are under-studied precisely because researchers usually prefer to focus on targets closer to clinical applications. Yet hidden among these overlooked elements could be the blockbuster drugs of the future. I discussed this challenge with Danish bioinformatician Søren Brunak and two winners of the first Telethon call dedicated to the dark genome. Enza Maria Valente and Silvia Nicolis both work in neurodevelopmental genetics, although they focus on different diseases. [NB: you won’t be surprised to know that CRISPR is one of the tools being used to shed light on genes that are still enigmatic even if the human genome is over 20 years old]

Craspases – surprising new CRISPR scissors are coming

3D portrait of Craspase (credit Ailong Ke)

The classic CRISPR system cuts DNA. Other variants cleave RNA. But now in the toolbox of new biotechnologies may come a tool that targets proteins: a CRISPR-driven caspase, already dubbed Craspase. What remains constant is that all these tools are programmable, thanks to the guide molecule that recognizes the desired target and directs the scissors there for editing. They are not paper shredders, rather they act like scalpels.

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The greatest functional map of all

Credit: Jen Cook-Chrysos/Whitehead Institute

Jonathan Weissman and colleagues used a CRISPR-based method to link each expressed human gene to its function in the cell. Here’s our suggested readings to learn more:
the paper in Cell by Josepg Replogle et al.
the Twitter thread by Joseph Replogle
MIT News (by Eva Frederick) and GenEngNews.

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.

Brenner, CRISPR and the zebrafish

“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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RNA moments

Soon after co-discovering the double helix, Francis Crick coined the term “central dogma of biology” to illustrate the flow of genetic information within biological systems. The basic idea is simple: DNA is the king of the cell, proteins are its major workforce, and RNA is a sort of a middle manager. He later admitted that dogma was a poor word choice for a rule that has exceptions. Indeed, he became one of the proponents of the RNA world hypothesis, where RNA is the primordial substance in the evolutionary history of life on Earth. We can only guess what the great British scientist might say about RNA taking the stage today.

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Organoids & CRISPR in the toolbox of virologists


Human gut organoids infected with SARS-CoV-2 (Credit: Joep Beumer/Hubrecht Institute)

“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.

Our CRISPR future, according to J. Doudna

The Nobel Prize for CRISPR is one of the most exciting ever assigned in chemistry and one of the most celebrated in the media, for reasons related to the invention and the inventors alike. On the one hand, the technique is changing the practice and the image of genetic engineering. On the other hand, Jennifer Doudna and Emmanuelle Charpentier are not merely great scientists; they are a success story in cracking the glass ceiling and a symbol of the strength of collaboration.

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Editing mitochondria

Click the links below to discover Ddda, the exceptional enzyme that allows mitochondrial editing, and celebrate curiosity-driven research.

The Nature paper by Joseph Mougous and David Liu: “A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing”

The news: “Scientists make precise gene edits to mitochondrial DNA for first time”

The news and views: “Mitochondrial genome editing gets precise”

The editorial: “Mitochondrial genome editing: another win for curiosity-driven research”