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.

Continue reading

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.

Continue reading

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?

Continue reading

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