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.

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

dogs-muscular-dystrophy

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