Evolving high fidelity CRISPR


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

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

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

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


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.

Adding the RNA string to the CRISPR bow


So far we have learned that CRISPR may turn a faulty gene off by cutting and mutating its sequence. But what if we want to proceed more cautiously and avoid permanent changes to the genome? We could leave the target gene intact but ineffective, by intercepting and destroying the RNA messages with which it gives the wrong orders to the diseased cells. In this way it would be easier to go back if necessary. The good news is that CRISPR is a jack-of-all-trades, well-suited for the task, and the new approach (call it RNA targeting with CRISPR) is going to help to study human biology and diseases. One of the technique pioneer, Feng Zhang, has demonstrated in Nature last week that it can efficiently target RNA in mammalian cells (and also plants), equalizing and even surpassing the performance of the current tool of choice for RNA knockdown (RNA interference). In short, besides advancing its career as DNA editor, CRISPR has also found a second job in the RNA business. Continue reading

An intelligence team for CRISPR warrior proteins

doudna_crispr_wide-cb9478286d39615ed64291ea95d4cfe022596aa2-s900-c85The University of Berkeley has opened a glimpse into the way bacteria use CRISPR, the microbial immune system that inspired the invention of the method for genetic modification also known as CRISPR. The paper published in Science by Jennifer Doudna’s team is a fascinating piece of basic research and scientists are hopeful they will be able to turn the discovery into a new biotech tool. Continue reading

CRISPR mosquitoes come to town

target malaria open days

The Italian city of Terni is now a spot on the map of cutting-edge research due to its new genetic-ecology lab,  which is getting involved in the Target Malaria project funded by the Bill & Melinda Gates Foundation. For a couple of days, citizens are allowed to visit the facility which is part of the Genomics, Genetics and Biology Innovation Pole. That’s an example of real public engagement: everybody can talk to researchers and watch videos, but also enter the climatic rooms simulating tropical conditions and see the cages for the insects which are the tiny heroes and the target of a daring scientific challenge. The mission here in Terni indeed is to investigate if the idea of controlling genetically malaria, by introducing self-destroying Anopheles gambiae into wild mosquitoes populations, is set to work in real world situations. Continue reading

Gene therapy meets CRISPR

gene therapyThe aim is engaging: to treat an increasing number of diseases by correcting the underlying genetic defects. And researchers are breathing optimism at last. The San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) in Milan has already treated 58 patients (including ADA-SCID, leukodystrophy, Wiskott-Aldrich syndrome and beta-thalassemia) and the count is approaching 300 worldwide. Moreover the promise of genome editing is looming on the horizon. We discussed the present and future of the field with the SR-Tiget director Luigi Naldini, who contributed to the latest report on human genome editing published by the US National Academies of Sciences and Medicine. Continue reading

Editing cancer at IEO

pelicci quadrotto

The second leg of the journey among leading labs takes us to the European Institute of Oncology in Milan. CRISPR’s potential is particularly exciting for oncology, as tumors are caused by multiple mutations and the new technique of genome editing is multiplexable, meaning it may target several genes at the same time. IEO scientific co-director Pier Giuseppe Pelicci has shared his enthusiasm with us.

“In our lab we are using CRISPR in 3 broad research areas. In the first area we follow the classic way, by disrupting the genes we want to study in order to understand their functions. CRISPR can do it much better than the previous techniques. It’s fast, very cheap and easy to handle. Before CRISPR we could carry out an experiment every 6 months, after CRISPR we can do one every week. It’s like altering the flow of time.” Continue reading