A decade of CRISPR is only the beginning

CRISPR past, present, and future according to the review by Jennifer Doudna and Joy Y. Wang just published in Science. This is the original caption: “The past decade of CRISPR technology has focused on building the platforms for generating gene knockouts, creating knockout mice and other animal models, genetic screening, and multiplexed editing. CRISPR’s applications in medicine and agriculture are already beginning and will serve as the focus for the next decade as society’s demands drive further innovation in CRISPR technology.”

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CRISPR aims straight for the heart

Photo credit Singularity Hub

The latest challenge is protecting damaged tissue immediately after a heart attack with the help of base editing (see the paper published in Science by Eric Olson’s group at the University of Texas Southwestern Medical Center). But there are hundreds of devastating diseases that affect the heart or other muscles and are caused by mutations that could be fixed by CRISPR-based tools (see this paper in Science Trsnslational Medicine for example). From Duchenne dystrophy to cardiomyopathies, some preliminary results are very encouraging.
Learn more reading the article on the Science paper published by El Pais and watching this video with Olson explaining his studies, especially on Duchenne muscular dystrophy.

Ode to Darwin, from Phages to Borgs

Phages first, Borgs then. Jennifer Doudna and Jill Banfield published surprising new findings in Cell, suggesting that thousands of phages have stolen CRISPR from bacteria to deploy it against rivals. “CRISPR is so popular even viruses may use it,” Science jokes. Nature puts it seriously “CRISPR tools found in thousands of viruses could boost gene editing.”

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Craspases – surprising new CRISPR scissors are coming

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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The human genome has no secrets

Twenty-one years after genome 1.0, the Telomere-to-Telomere Consortium gives us a new assembly (T2T-CHM13) generated by long-read sequencing. It adds approximately 200 megabases of accurate genetic information, roughly equivalent to a whole chromosome. As Deanna Church writes in a perspective it is “an important step to assembly models that represent all humans, which will better support personalized medicine, population genome analysis, and genome editing”. Dont’s miss this Science issue!

The ever-expanding CRISPR toolbox

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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CRISPR tracks metastatic progression

Phylogenetic trees of tumors and metastases can reveal key features such as the clonality, timing, frequency, origins, and destinations of metastatic seeding. Each color in the image above represents a different location in the body. A very colorful tree shows a highly metastatic phenotype, where a cell’s descendants jumped many times between different tissues. A tree that is primarily one color represents a less metastatic cell. Credit Jeffrey Quinn/Whitehead Institute

CRISPR-based techniques allow the reconstruction of the “family tree” of the cells that compose an animal’s body by marking them with a pattern of deletions and insertions. This kind of barcoding has already helped trace embryo growth and organoid development and is shedding light on essential oncology questions by catching cancer in the act. Read how “Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts” in this Science paper and the news from Whitehead Institute.

A bold proposal and a cautious report

Let’s imagine a hundred or more citizens from all over the globe, selected to partecipate in a giant focus group aiming to represent world views. It would be an unprecedented social experiment, that’s for sure, but the call is worth considering. The bold proposal comes from a group of social scientists and a few geneticists (George Church included) writing today in Science. Fascinating as it is, this kind of assembly is probably easier said than done. However, the main problem, in my opinion, comes next: what should experts and politicians do with the assembly’s deliberations?

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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.