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”

Edited shells turn left

snail crispr cover

Most snails live in right-coiled shells, and the general rarity of sinistral gastropods has long attracted comment and wonder, according to the late Stephen Jay Gould. “Aristotle declared them impossible, but d’ Argentville called them uniques, while Geoffroy dubbed them nonpareilles. Since no one has ever developed an even vaguely plausible argument for dextral advantage, the overwhelming predominance of right-handed coiling among gastropods has been a persistent puzzle.” Continue reading

Harvard breaks the record for multiple editing

dna colorato“Wow! Badass. 13,200 crispr base edits in a single cell! On the way to ‘recoded’ human cells,” tweeted Antonio Regalado before covering the news in MIT Technology Review. To be honest, the radical redesign of species is still sci-fi dystopia, but the paper preprinted by Cory J. Smith et al. in bioRxiv is impressive anyway. Continue reading

CasX: the smaller the crispier

cas treeTime will tell if it is going to become the preferred enzyme for genome editing or just another useful tool in the expanding CRISPR kit. But the future of CasX looks bright. It is much smaller than the nucleases that have provided a foundation for this technology. Being fewer than a thousand amino acids, it offers clear advantages for delivery in comparison with Cas9, that is over 1,300 Aa. Continue reading

CRISPR best and worst in 2018

CRISPR contributed to Science’s Breakthrough of the Year and was also nominated for the Breakdown category by the same journal. The second nomination was an easy guess: He Jiankui and its baby-editing claim were also mentioned in Nature’s 10 for 2018. Much more interesting is the decision to celebrate cell-barcoding, the CRISPR-based technique used to track embryo development in stunning detail and over time. Continue reading

CRISPR meets machine learning

If a donor template is not provided when CRISPR cuts the DNA, broken ends are fixed by natural repairing mechanisms in a way that is considered stochastic and heterogeneous. This makes template-free editing impractical beyond gene disruption, right? Wrong, according to a study published in Nature by Richard Sherwood and colleagues. Continue reading

Picture of the week

bimaternal pups

Healthy adult bimaternal mouse (born to two mothers) with offspring of her own.
Credit: Leyun Wang

Single-gender worlds will remain a sci-fi fantasy. Gay and lesbian couples won’t become parents this way for the foreseeable future. This kind of manipulation is just too risky for humans. But unisexually reproducing mice are an impressive accomplishment, and CRISPR stands out again as a powerful research tool, opening up brand new possibilities for the study of genomic imprinting. For further details, please see the STAT News article about the Cell Stem Cell paper by Zhi-Kun Li.