Harvard breaks the record for multiple editing

dna colorato“Wow! Badass. 13,200 crispr base edits in a single cell! On the way to ‘recoded’ human cells,” tweeted Antonio Regalado before covering the news in MIT Technology Review. To be honest, the radical redesign of species is still sci-fi dystopia, but the paper preprinted by Cory J. Smith et al. in bioRxiv is impressive anyway. Continue reading

CasX: the smaller the crispier

cas treeTime will tell if it is going to become the preferred enzyme for genome editing or just another useful tool in the expanding CRISPR kit. But the future of CasX looks bright. It is much smaller than the nucleases that have provided a foundation for this technology. Being fewer than a thousand amino acids, it offers clear advantages for delivery in comparison with Cas9, that is over 1,300 Aa. Continue reading

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

CRISPR meets machine learning

If a donor template is not provided when CRISPR cuts the DNA, broken ends are fixed by natural repairing mechanisms in a way that is considered stochastic and heterogeneous. This makes template-free editing impractical beyond gene disruption, right? Wrong, according to a study published in Nature by Richard Sherwood and colleagues. Continue reading

Picture of the week

bimaternal pups

Healthy adult bimaternal mouse (born to two mothers) with offspring of her own.
Credit: Leyun Wang

Single-gender worlds will remain a sci-fi fantasy. Gay and lesbian couples won’t become parents this way for the foreseeable future. This kind of manipulation is just too risky for humans. But unisexually reproducing mice are an impressive accomplishment, and CRISPR stands out again as a powerful research tool, opening up brand new possibilities for the study of genomic imprinting. For further details, please see the STAT News article about the Cell Stem Cell paper by Zhi-Kun Li.

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.

CRISPRing the Neanderthal’s mind

Neanderthal_minibrains

Sapiens vs Neanderthalized brain organoids (credit A. Muotri)

Taking a peek into the brain of a Neanderthal specimen would be a dream for whoever is interested in the evolution of human intelligence. To get an idea of the cognitive abilities of our closest relatives, so far, anthropologists and neuroscientists could only study the fossil and archaeological record, but a new exciting frontier is opening up where paleogenetics meets organoids and CRISPR technologies. By combining these approaches, two labs are independently developing mini-brains from human pluripotent stem cells edited to carry Neanderthal mutations. Alysson Muotri did it at UC San Diego, as Jon Cohen reported in Science last week. Svante Pääbo is doing it at the Max Planck Institute in Leipzig, as revealed by The Guardian in May. Forget George Church’s adventurous thoughts on cloning Neanderthals. The purpose here is to answer one of the most captivating questions ever asked: did the mind of these ancient men and women, who interbred with our sapiens ancestors before going extinct, work differently from ours? Last but not least, with respect to the ethics of experimenting with mini-brains, don’t miss the perspective published in Nature.