CRISPR-GPT: a copilot for editing

Nature Biomedical Engineering has introduced a chatbot specifically designed to help beginners with their first experiments and to support experienced researchers in their work.

Since it was first described in Science in 2012, in the landmark paper by Emmanuelle Charpentier and Jennifer Doudna, the success of the CRISPR technique has been summed up with a handful of adjectives: cheap, precise, easy to use. But since everything is relative, it’s worth asking: how easy, and compared to what? When measured against previous genetic editing platforms, CRISPR is far simpler to apply. Whereas only a few highly specialized centers could once perform these experiments, with CRISPR a standard lab, the basic skills of an ordinary biologist, and solid familiarity with bioinformatics may be enough. Still, novices need guidance, and even seasoned researchers can run into problems.

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Evolving a new CRISPR system to insert genes

evoCAST (credit: George Lampe)

Recently, David Liu won the Breakthrough Prize for inventing two tools for precise, small-scale genome editing (base editing and prime editing). However, in some cases, rather than correcting a mutation within a defective gene, it may be more practical to insert a fully functional copy of the gene. That’s the mission of evoCAST, the latest invention from the Broad Institute near Boston, a hub for next-generation CRISPR tools.

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An RNA bridge for genome design

When small tweaks aren’t enough and massive DNA interventions are needed, a new biotech tool inspired by a peculiar class of jumping sequences may come to the rescue.
Barbara McClintock discovered mobile genes in the 1940s, and since then these transposable elements have never ceased to amaze.

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Next-Gen CRISPR – pasting whole genes without cutting

PASTE is a three-part CRISPR tool invented at the MIT McGovern Institute for Brain Research. It’s composed of a modified CRISPR-Cas9 (it’s called nickase because it nicks a single DNA strand instead of cutting both) and two effectors: RT stands for reverse transcriptase (just like in prime editing) while LSR means large serine recombinase.

This brand-new molecular machine writes the genome in three steps. Step 1: the nickase finds the desired site. Step 2: the reverse transcriptase inserts a landing pad. Step 3: the recombinase lands there and delivers its large DNA cargo. The aim is to replace whole genes, when fixing mutations is not enough (one example is cystic fibrosis). Here are the links to learn more:

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MetaCRISPR, how to edit microbiomes

Jill Banfield and Jennifer Doudna (photo by Keegan Houser)

The best way to summarize the new metaCRISPR approach, recently published in Nature Microbiology, is the Twitter thread by Jill Banfield:

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Feng Zhang on how transposons hijacked CRISPR

CRISPR pioneer Feng Zhang walked through his current research projects at the national meeting of the Italian Genetics Association (AGI) on September 24. CRISPR associated transposases, retrovirus-like particles repurposed as delivery vehicles, the ancestry of CRISPR systems, and more. The first issue is probably the most fascinating. It’s actually amazing to see a new activity performed by some CRISPR systems: not to protect bacteria from viruses, but to help transposons jump into specific genome sites.

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