Your Missing Links Are Here (15 January 2021)

Top picks

• Editas Medicine announced this week that it has obtained (FDA) approval for the first clinical trial for EDIT-301, an ex vivo one-time autologous (patient-derived) treatment for sickle cell disease. EDIT-301 is the first CRISPR-Cas12a-engineered cell therapy to enter clinical development.
• Using CRISPR screens, researchers in the US found that G protein–coupled estrogen receptor 1 (GPER1), which is expressed in foetal tissues, suppresses type I interferon (IFN) immune responses in the placenta to protect the foetus from maternal infection. The findings were recapitulated in pregnant mouse models of infection, suggesting GPER1 as a potential therapeutic target to protect developing foetuses from maternal and fetal infections.

Research

• Researchers at John Innes Centre in Norwich, UK have used CRISPR to create a recombinant (bacterial) strain of Streptomyces formicae with 10x fold increased production of naturally-occurring formicamycin antibiotics. Next steps include understanding the mechanisms of action of these antibiotics, which are capable of killing the toughest superbugs in lab conditions. The work was published this week in Cell Chemical Biology.
• Researchers from China and Denmark show that targeting herpes simplex virus 1 with CRISPR–Cas9 blocks viral replication and cures herpetic stromal keratitis (herpes infection of the cornea) in mice.
• Researchers have used surface antigen-guided CRISPR screens to identify genes that regulate myeloid leukemia differentiation. Lack of cellular differentiation is a hallmark of acute myeloid leukemia (AML), and identifying factors that regulate differentiation may reveal new therapeutic strategies for AML.

Industry

• Editas Medicine's Chief Scientific Officer Charles Albright leaves for new job at an early-stage company just as Editas gets FDA green light for CRISPR sickle cell therapy trial.
• US-based biotech startup Tessera Therapeutics announced that it has raised more than $230 million in its second round of funding. The company was founded just 2 years ago and is pursueing a new technology gene writing for the treatment of genetic diseases.
• KSQ Therapeutics and Takeda enter broad strategic collaboration to desearch, develop and commercialize novel immuno-oncology therapies. The envisioned cell and non-cell therapy products will modulate targets to be identified using KSQ’s CRISPRomics discovery platform technology.
• French biotech Eligo Bioscience strikes deal with GlaxoSmithKline aimed at advancing Eligobiotics® for the treatment or prevention of acne vulgaris with a pioneering CRISPR-based therapeutic for strain-specific microbiome modulation.
• Verve Therapeutics, US, selects its base editor candidate VERVE-101 as lead program to treat heterozygous familial hypercholesterolemia. The decision came following durable and consistent lowering of blood low-density lipoprotein cholesterol after a one-time treatment in non-human primates.
• Sarepta Therapeutics and Genevant Sciences annouce new research collaboration to develop lipid nanoparticle-based gene-editing therapeutics. The venture will bring together Sarepta’s proprietary gene-editing technology and Genevant’s proprietary LNP delivery platform for several neuromuscular diseases including Duchenne muscular dystrophy.
• Mammoth Biosciences secures award to develop CRISPR-based diagnostics and biosurveillance platforms. The new funding, which comes with a subcontract with MRIGlobal, will allow Mammoth to develop its robust DETECTR™ platform for CRISPR-based detection of emerging biological threats.

Vision and opinion

• CRISPR patent war between the Broad Institute and the University of California Berkely gets 7^th place in the "Top Patent Law Stories of 2020" from Patent Docs blog, JD Supra.

COVID-19

• New research published in Cell reports the use of genome-wide CRISPR screens identify host viral entry factors and host pathways required for infection by SARS-CoV-2 and common cold coronaviruses.

Meetings, webinars and podcasts

• In the latest Milken Institute podcast, Nobel Laureate Jennifer Doudna chatted with host Mike Milken about how fundamental research in academia led to a quick COVID-19 vaccine, and more. Listen to the podcast here, and read the podcast transcript here.

Safety

• Recent article published in Methods Molecular Biology presents detailed protocols for evaluating the specificity of CRISPR-Cas9 and related gene-editing approaches in cells using targeted as well as unbiased approaches which are able to identify off-target cleavage events throughout an entire genome.
• crisprSQL: a novel database platform for CRISPR/Cas off-target cleavage assays. This new resource from the University of Oxford is an interactive and bioinformatically enhanced collection of CRISPR-Cas9 off-target cleavage studies for cleavage profiling, gene editing safety analysis and transcriptomics. You can find the crisprSQL database here.

Review

• Anti-CRISPRs go viral: the infection biology of CRISPR-Cas inhibitors. This review discusses recent developments in the study of anti-CRISPR (Acr) proteins and propose a framework of “phage autonomy” to evaluate CRISPR-immune evasion strategies. Read our related interview about how exploitation of anti-CRISPR proteins might make gene therapy safer.
• CRISPR/Cas9 for the treatment of haematological diseases: a journey from bacteria to the bedside. This review focuses primarily on blood diseases, and takes us through the timeline of important events from the discovery of CRISPR in bacteria to the first in vivo CRISPR clinical trial.

Heh, huh wow

• DNA hard drives? Scientists use an engineered redox-responsive CRISPR system to store digital data in CRISPR arrays inside the genomes of living bacterial cells.