CMN Weekly (4 June 2021)

Top picks

• Research published in Nature this week reveals base editing as a potential cure for sickle cell disease (SCD). Correction of a single mutation in the β-globin gene – which is the single cause of SCD - with base editing resulted in a non-pathogenic protein variant that had promising therapeutic effects in mice. Read the full story in our interview with David Liu who was involved in this work.
• American senate confirms Eric Lander to lead White House science shop. Lander has held prominent roles in U.S. research and science policy, including former president and founding director of the Broad Institute, and co-leader of the public Human Genome Project to the completion of a first draft in 2001.

Industry

• San Francisco- and Asia-based Engine Biosciences secures $43million in a Series A funding round, and maps out its plans for the next 2 years with hopes to initiate the first clinical trials in 2023. Engine uses bioinformatics-based machine learning to identify disease-causing mutations and aims to fix them with precision therapeutics.
• Diagnostics start-up Scope Biosciences (Netherlands) has been awarded an Atlas Invest Entrepreneurship Start-Up Award of €35.000. The Wageningen University spinout is developing a CRISPR-Cas based diagnostic platform Scope Dx for rapid point of care diagnostic solutions. Current projects include a SARS-CoV-2 assay to detect COVID-19.
• Twist Bioscience partners with Vivlion to generate gRNA libraries for CRISPR applications. The move brings together Twist’s capacity to generate highly uniform long oligos at scale with Vivlion’s ability to translate these into equally highly uniform CRISPR libraries for the next generation of high-throughput CRISPR screens.
• The non-profit partnership CARB-X is awarding up to US$1.82 million to Paris-based Eligo Biosciencewith additional funding up to US$7.05 million pending milestones. The funding will be used to develop a new class of highly specific bacteriophage- and CRISPR-based therapeutics to selectively kill extended-spectrum beta-lactamase-producing and Carbapenem-resistant E. coli and K. Pneumoniae from the microbiome of transplant patients.
• Precision BioSciences announces a new study in Nature Communications using its engineered ARCUS meganuclease to target mutant mitochondrial DNA in vivo in a mouse model. More details in the company’s press release here.

Research

• US-based scientists working with gene drives have developed SPECIES - Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species. This tool, which was described yesterday in Nature Communications, uses CRISPR to engineer so-called SPECIES, e.g., certain fly species that can be further engineered to carry gene drives – but which are genetically incompatible with each other and cannot reproduce. The team showed that SPECIES can be used as confineable gene drives to replace wild-type populations in a threshold-dependent manner. Applications for SPECIES include pest control on food crops and control of insect disease vectors.
• Australian team finds that CRISPR-Cas9 deletion of the adenosine A2A receptor enhances CAR T-cell efficacy in murine and human-derived CAR T-cells, by abrogating the immunosuppressive effects of adenosine without deleterious effects on memory phenotype or CAR T-cell persistence. The findings were recently published in Nature Communications.
• Researchers in Germany show that non-canonical crRNAs derived from host transcripts can be programmed to enable multiplexable RNA detection by Cas9. The discovery formed the basis for LEOPARD, a new CRISPR diagnostic method that can detect many biomarkers at once. The findings were published recently in Science.
• A team in Japan has found that Cas10d is a functional nuclease in the type I-D CRISPR Cas system, and that it can be used for targeted bi-directional long-range deletions and short insertions/deletions in genomic DNA in human cells. The findings were published in Nucleic Acids Research yesterday.

Delivery

• Researchers at University of California, Berkeley, have developed a one-step strategy using engineered lentiviral particles to introduce Cas9 ribonucleoproteins (RNPs) and a CAR transgene into primary human T cells without electroporation. The findings, published in Cell Reports this week, create new possibilities for complex genetic engineering of immunotherapies.
• Scientists in China have developed AdBlue, a novel system for the construction of recombinant adenoviruses using an enzymatic assembly strategy. AdBlue could significantly reduce the time and labour required to generate adenoviral vectors for delivery of CRISPR gene-editing reagents. The results were published in CRISPR Journal this week.

COVID-19

• Montana State University researchers develop CRISPR-based coronavirus rapid test that can accurately detect even relatively small amounts of coronavirus in patient samples in less than 30 minutes and sometimes in as little as one minute. The new tool is based on target RNA recognition by a type III CRISPR complex, which triggers Cas10-mediated polymerase activity, leading to the simultaneous generation of pyrophosphates, protons and cyclic oligonucleotides that are easily detected using colorimetric or fluorometric readouts. The findings were published in Cell Reports Medicine last week.
• Sherlock Biosciences announces initial results of automation study with NorDx Laboratories on CRISPR-based SARS-CoV-2 test. The study was the first successful automation of a CRISPR test for high-throughput, and paves the way for thousands of tests per day on a single system.

Webinars and conferences

• The CRISPR 2021 meeting is running now and until the 10th June. See the event's website for more information.
• CRISPR Medicine News hosted a webinar on CRISPR Delivery Systems last week. In case you missed it, you can still watch it using our on-demand function. CMN+ subscribers can access our on-demand webinars here.
• CRISPR Functional Genomics Symposium hosted by 10x Genomics and MilliporeSigma is on from June 28th-July 1^st. Register for the event here.

Review and analysis

• Toward the correction of muscular dystrophy by gene editing: Review by Eric Olson, leading researcher in Duchenne muscular dystrophy (DMD), on recent work from his lab and others toward the genetic correction of DMD and the opportunities and challenges in the path to clinical translation. Last month, Eric Olson spoke with us about his recent work demonstrating that editing of a single nucleotide in the DMD gene could restore dystrophin production and myocyte function in DMD.

• Therapeutic Genome Editing and In Vivo Delivery: This review provides a summary of the mechanisms of genome editing, why CRISPR-Cas9 attracts so much attention compared to other engineered nucleases, current progress in CRISPR-Cas9 delivery, and the pre-clinical and clinical applications of CRISPR-Cas9.

Heh, huh wow

• Burnt toast could soon be a thing of the past in the UK, with British gene-editing public consultation announcement on genetically-modified wheat expected mid-June.