Category Archives: In the lab

Craspases – surprising new CRISPR scissors are coming

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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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MetaCRISPR, how to edit microbiomes

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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

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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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The ever-expanding CRISPR toolbox

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Credit: Mon Oo Yee/Innovative Genomics Institute

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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Toward an NIH-validated CRISPR toolkit

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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”.

Evolving high fidelity CRISPR

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ANNA CERESETO BISTURI GENOMICO BIOMEDICINA

credit Alessio Coser

It’s called evoCas9, and it’s the most accurate CRISPR editing system yet, according to a study just published in Nature Biotechnology. Researchers at the University of Trento, in northern Italy, induced random mutations in vitro on a piece of a bacterial gene coding for the DNA-cutting enzyme (the REC3 domain of SpCas9) and then screened the mutated variants in vivo in yeast colonies by looking at their color. If the molecular scissors work properly, cutting only the right target, the yeast becomes red, but colonies are white if CRISPR cuts off target. Continue reading →

Rec-Stop-Play: CRISPR becomes a biological recorder

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biological recorder 2When using a standard tape recorder you just have to press the buttons. Now a Columbia University team has devised a system for doing the same in living systems, recording changes taking place inside the cells. How does it work? This biological recorder, described in a study appearing in Science, is called TRACE and may help us chronicle what happens in open settings such as marine environments or in habitats difficult to access such as the mammalian gut. It records molecular fluctuations instead of sounds, capturing metabolic dynamics, gene expression changes and lineage-associated information across cell populations. The medium is DNA rather than magnetic tape. Sequencing is like playing. But how is the DNA recording done? Continue reading →

CRISPR Express: nanovectors are coming

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nanoparticle MIT[1423]Suppose you have developed the winning weapon to defeat certain genetic diseases by reliably correcting pathogenic mutations. There is still a problem: how do you march onto the battlefield, inside sick cells? The weapon is the genome-editing machinery, and the most efficient vessel ever tested are lipid nanoparticles. With this approach, described in a study published in Nature Biotechnology last week, CRISPR has beaten its success record in adult animals, knocking out the target gene in about 80% of liver cells. Continue reading →

Testing the future of beer

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birraThe Daily Beast has misunderstood, unfortunately, and the rose-scented CRISPR beer does not exist yet. But researchers are hopeful to try it in pilot-scale in the near future. A team from the University of Leuven in Belgium has identified two genes that could be used to generate novel flavor profiles in alcoholic beverages. They are called TOR1 and FAS2 and work by increasing the production of phenylethyl acetate in yeast (Saccharomyces cerevisiae). CRISPR helped to swap the scented alleles into standard strains, which suddenly began producing more floral aromas. Continue reading →

Two big cheers for base editing

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MUTATION

The rising star of base editing shadowed classic genome editing last week. I’m sure you heard about the ground-breaking papers respectively published by David Liu and Feng Zhang in Nature and Science. CRISPR enthusiasts have probably already enjoyed the piece by Jon Cohen on the new approach, i.e., the rearrangement of atoms in individual DNA letters to switch their identity without even cutting the DNA strands. But let’s take a look also at The Scientist, which runs two must-read articles about the details of the experiments. The first take-home message is the latest achievements are exciting, but base editors are not better than CRISPR, they’re just different. The second one, there is still room for improvement with base editing, and the best is yet to come.