Epigenetic editing hits hat-trick

editing epigenetico Cell

Reversing three genetic diseases in the animal model without even changing a single DNA letter. A Salk Institute team did it by bringing together two of biomedicine’s hottest trends. One is the CRISPR technique, which edits target genes through a programmable molecular machine named Cas9. The other is epigenetics, i.e., the study of chemical modifications that switch genes on and off without altering their sequence. It’s called epigenetic editing, because corrections are precise as in manuscript revision and occur at a level that is over (epi- in Greek) genetics. Continue reading

Gene drives: the experiment goes social

harvard-mag-pete-ryanChoose a word to fill the gap in the sentence. “Gene drives are an ambitious experiment in …”. Genetics? Ecology? Evolution? Obviously, gene drives are all this and more. They may also represent a significant social experiment in risk communication, public engagement, participatory processes. Potential applications of this technology include controlling the transmission of vector-borne diseases and eliminating invasive species from sensitive ecosystems. We do not yet know if these genetic elements, designed to foster the preferential inheritance of a gene of interest with CRISPR’s help, will work in field trials as hoped. To find out, a green light to test this technology out of the labs will have to be negotiated with the public, stakeholders, regulators, and governments of affected countries. A first step in this direction was taken last week with the commitment to respect shared guiding principles in gene drive research and communication published in Science by the technology main sponsors and supporters. Signatory organizations are scattered around the world, from the US to India, with the Bill & Melinda Gates Foundation at the forefront with its Target Malaria project. Continue reading

Zinc fingers grab CRISPR for once

sangamo tweetThe first patient edited “in vivo” last week is a breaking news story, and zinc finger nuclease ZFN must be credited for the accomplishment. A putatively outdated system stealing the scene from the most celebrated technique for gene editing is a bit like Carl Lewis beating Usain Bolt at the Rio Olympics. Any wonder that tweets by some biotech-enthusiasts had something of a derby atmosphere, while many inattentive readers thought it was CRISPR stuff, as lay people never heard of ZFN before. 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

Adding the RNA string to the CRISPR bow

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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

China did it once again

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Junjiu Huang is back. Two years later, Protein & Cell publishes another study by the team which first edited human embryos in 2015 sparking uproar. They targeted the gene responsible for beta thalassemia, once again. This time, however, in place of using embryos discarded by fertilization clinics, they resorted to cloning. Furthermore, Huang and colleagues employed a CRISPR variant called base editor changing a single DNA letter without even cutting the double helix. The news is circulating among experts but has not yet attracted the media spotlight. Stem cell specialist Alessandro Bertero has brought it to the attention of CRISPeR Frenzy. According to the researcher involved in the British experiment just published in Nature, the latest paper from China is far from perfect but it’s quite interesting anyway (see his technical comment below). Continue reading

Editing embryos, the British way

embrioni UK.docxThey are the first human embryos edited in Europe and reported in scientific literature. The key difference with experiments already carried out in China and US is that the research published by Nature last week doesn’t have embryonic gene therapy in view. The London Francis Crick’s Institute team, in fact, was not interested in correcting disease-causing mutations but in increasing knowledge on human embryonic development. We asked one of the authors, Alessandro Bertero, to explain goals and results. The Italian researcher was pursuing his Ph.D. at Cambridge when he helped to refine the technique used by Kathy Niakan and colleagues to edit the genome of embryos. He answered our questions via Skype from America, where he continues working on embryonic stem cells as a postdoctoral fellow at Washington University Continue reading