The fastest CRISPR has a photoswitch

Very fast CRISPR activated by light [Credit: Ella Marushchenko]

Genome editing + optogenetics = very fast CRISPR (vfCRISPR). Two revolutionary techniques meet in the paper by Yang Liu and colleagues just published in Science. The Johns Hopkins University team developed a caged RNA strategy that allows Cas9 to bind DNA but needs light at wavelengths that are not phototoxic to activate cleavage. The cut is immediate upon light exposure, offering scientists a way to study DNA repair from its start. The process is so precise that one allele of a gene can be edited at a time, allowing the generation of heterozygous mutations for studying complex genetic traits. See also the perspective by Darpan Medhi and Maria Jasin in Science.

CRISPR in the news

CAR-T cell therapy meets CRISPR. See the results from the first US trial of gene editing in patients with advanced cancer, just published by Carl June and colleagues in Science, together with a perspective by Jennifer Hamilton and Jennifer Doudna and a piece of news by Jennifer Couzin-Frankel. We still don’t know if edited T cells are effective against cancer, but this Phase 1 clinical trial suggests the approach is safe and feasible.
RNA editing takes off. Take a look at the news feature by Sara Reardon in Nature. It’s a four pages introduction to ADAR, an alternative to CRISPR for flexible, reversible therapies.

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

Ag research or biowarfare?

corndrought“Agricultural research, or a new bioweapon system?”. This is the question asked by Guy Reeves et al. in a policy forum published in Science today. The evolutionary geneticist from the Max Planck Institute and his German and French coauthors doubt that the Insect Allies program funded by Darpa in the US will realize significant agricultural benefits, e.g. in relation to drought, frost, flooding, herbicide, salinity, or disease. They fear, indeed, that it will be “widely perceived as an effort to develop biological agents for hostile purposes and their delivery, which – if true – would constitute a breach of the Biological Weapons Convention.” Continue reading

Anti-CRISPR and the Red Queen

red queen

The battle for survival between bacteria and bacteriophages can be framed according to the Red Queen hypothesis. To avoid extinction bacteria must evolve new mechanisms of resistance, such as CRISPR immunity. Viruses, in turn, must evolve countermeasures to inactivate these resistance mechanisms, such as anti-CRISPR proteins. These natural inhibitors may well become biotech tools useful to keep genome-editing in check and are a minefield waiting to be explored. Jennifer Doudna and Joseph Bondy-Denomy used bioinformatics to find some of them, and have just published their findings in Science. Paraphrasing Dobzhansky’s famous dictum, nothing in biotechnology makes sense except in the light of evolution.

Cutting off Duchenne in dogs. How excited should we be


credit: Royal Veterinary College, University of London

“Exciting news! Our partner, Dr. Eric Olson and his team at Exonics published their research on increasing dystrophin restoration of 92% in the hearts of dogs. While they have a long way to go, their dramatic research gives hope to all families affected by Duchenne!”. This is how the patient advocacy group CureDuchenne announced the CRISPR breakthrough just published in Science. Continue reading

Playing a three of CRISPR kind

three acesIt is Science but it could be mistaken for The CRISPR Journal. The latest issue indeed runs three papers by three CRISPR aces – David Liu, Jennifer Doudna, and Feng Zhang – about the cutting-edge fields of biological recorders and advanced diagnostic tests. 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

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