Your Missing Links Are Here (5 March 2021)

Some of the best stuff we picked up around the internet

By: Gorm Palmgren - Mar. 5, 2021

Researchers at Genethon, France, have used simultaneous CRISPR-based knock-in and knockout to treat a group of blood disorders, β-thalassemia, caused by mutations in the β-globin gene cluster. The approach upregulated β-globin expression while downregulating expression of α-globin, thereby restoring the balance between adult haemoglobin's two components. You can read our interview with the paper's senior author, Mario Amendola, here.
A new class of C:G to G:C base editors have been developed by researchers from Singapore. The base editors consist of a nickase-Cas9 fused to a cytidine deaminase and base excision repair proteins, and they target cytidine in WCW, ACC or GCT sequence contexts with a mean efficiency of 15.4% without selection.

"PnB Designer" is a new web-based design guide to prime and base editor RNAs for animals and plants. The user-friendly design tool is developed by researchers from ETH Zürich in Switzerland.
Light-mediated deactivation of Cas9 and base editors within seconds has been achieved with photocleavable guide RNAs. The researchers from Johns Hopkins University, USA believe their approach can be valuable for precision genome editing and DNA damage and repair studies.
A new set of tools have been established to standardise phage host prediction based on CRISPR spacers. The researchers from Université Laval in Québec City, Canada, will use the approach to discover as yet unknown phages and demonstrated their use for the identification of phages that infect gut-associated bacteria.
A new lipid nanoparticle (LNP) delivery system for Cas9 mRNA and guide RNA to the liver is more efficient than previous LNPs. The system was tested in mice by editing the Angptl3 that helps break down cholesterol, and it managed to lower LDL cholesterol by up to 57%.
PEGylated polyplex micelle (PM) have been used successfully to co-deliver Cas9 mRNA and sgRNA to the mouse brain. Co-encapsulating the two RNAs in one PM prevented sgRNA release upon dilution and thus decreased its enzymatic degradation.

Cellectis announced in a quarterly business update and financial report a cash position of $274 million as of the beginning of the year and a cash runway into late 2022. Three Cellectis-sponsored phase 1 clinical trials are ongoing, and a new collaboration with Cytovia Therapeutics to develop TALEN gene-edited iPSC-derived NK and CAR NK cell programs.
Caribou Biosciences announced the successful completion of a $115M Series C financing. The financing will be used to develop further the Company's proprietary, next-generation CRISPR technology platform and to advance the Company's pipeline of wholly-owned allogeneic immune cell therapies for oncology with best-in-class potential.
If you plan to invest in CRISPR Therapeutics, you might want to read this piece in Seeking Alpha. It presents a thorough evaluation of the Company's clinical trials pipeline and its market potentials.

Innovative Genomics Institute has made an updated overview of ongoing CRISPR clinical trials. The overview includes a list of current trials and takes a look into the future and suggsts what to watch for. You might also want to dive into our comprehensive database of clinical trials here.

Computer engineers from Cyprus have used convolutional neural network-based deep learning to predict CRISPR/Cas12 gRNA activity. According to the researchers, this will help choose the best gRNA for detecting COVID-19 virus using the CRISPR-Cas12 system. In line with this approach, a Chinese minireview looks at the use of CRISPR-Cas12a for biosensing and gene regulation.

"Precision Engineering of the Genome, Epigenome and Transcriptome" is the title of a Virtual Keystone Symposia taking place 8-10 March. You can register for the event here.
The New York Academy of Sciences has arranged a webinar entitled CRISPR: New Frontiers for 15 March. You can register for the webinar here.

Persons and prizes

The Pezcoller Foundation has awarded the Award for Extraordinary Achievement in Cancer Research (AACR) to Hans Clevers. Clevers is a group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research in Utrecht, the Netherlands, and has pioneered research in the Wnt-signalling pathway and its contribution to colon cancer onset and progression. You can read our interview with Hans Clevers here.

A review in Nature Reviews Urology considers the potential for gene-based therapy in prostate cancer. Although no clinically relevant outcomes have yet appeared, the review finds great promise for gene therapy to become established in prostate cancer care in the future.
Another review in the journal 3Biotech takes a closer look at CRISPR and its role in cancer approaches and applications. The review also presents an overview of the clinical trials associated with translating CRISPR/Cas9-based therapy.
"Small Nucleic Acids and the Path to the Clinic for Anti-CRISPR" is the title of a review in Biochemical Pharmacology. The review discusses the use of inhibitors to act as a failsafe or adjuvant to reduce off-target effects in patients.
A review in BioDrugs summarises the current approaches that use CRISPR to facilitate off-the-shelf CART products, increase CART-cell efficacy, and minimise CART-associated toxicities.

A piece by Isaac Walter Isaacsson - the author of the upcoming book The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Rac‪e‬ - describes a race between Jennifer Doudna and Feng Zhang to develop an easy-to-use CRISPR-based Covid-19 test. The piece also mentions the bitter CRISPR patent fight between the two scientists.
Another piece in ScienceNews.dk debates the idea of correcting genetic mutations in human embryos. The debate takes off from an original study presented in Cell by researchers from Columbia University, New York, and subsequently commented by Eva Hoffmann from the University of Copenhagen, Denmark.
On YouTube, you can watch a new, one-hour long Dr Stanley Ho Memorial Lecture with Jennifer Doudna about CRISPR-Cas9: Genome Editing and the Future of Medicine.

Heh, huh, wow

CRISPR has been used for knockout of the asparagine synthetase gene, TaASN2, of wheat. The feat yielded grains with 90% reduced levels of free asparagine. Free asparagine is the precursor for acrylamide - a suspected carcinogen - which forms during the baking, toasting and high‐temperature processing of foods made from wheat.