CMN Weekly (1 October 2021)
By: Gorm Palmgren - Oct. 1, 2021
- Editas Medicine has announced positive initial clinical data from its ongoing phase 1/2 clinical trial of a CRISPR-based treatment, EDIT-101, for Leber congenital amaurosis 10 (LCA10). EDIT-101 offers in vivo editing of CEP290 after retinal injection. The treatment was well-tolerated, and most patients showed efficacy signals suggesting productive editing and signs of improved vision. The results, however, did not impress investors and led to a 20% decrease in Editas' stock price.
- A team of researchers from the University of California, Berkeley has developed a technique to identify protein domains that can be deleted without losing the protein's function. This has been used to establish that large deletions in four domains of catalytically-dead Streptococcus pyogenes Cas9 are tolerated and thus facilitate viral delivery of a minimal, DNA-binding effector protein.
- A new integrated pipeline dubbed STAMPScreen allows researchers to identify genes of interest and perform genetic screens without guessing which tool to use or what experiments to perform to get the results they want. The tool can, e.g., be used to compare the performance of CRISPR activation or inactivation and cDNA overexpression in hiPSCs.
- A novel sensitive and specific method for detection of human norovirus genotype GII.4 - a common cause of gastroenteritis - without the need for ancillary equipment is described by researchers from China. The method employs CRISPR-Cas12a combined with reverse transcription recombinase polymerase amplification.
- Researchers from Iran have developed a potential new cheap and environmentally friendly non-viral delivery method for CRISPR-plasmids. The technique employs calcium- and chitosan-based nanomaterials and has so far only been tested for its successful capability of transfecting HEK-293 cells with eGFP-plasmids.
- In a paper in Nature, American and Dutch researchers have provided a high-resolution mechanistic explanation for the PAM-dependent spacer-acquisition process in Cas4-containing CRISPR systems. The results show that Cas4 is a dedicated PAM-cleaving endonuclease tightly regulated by the Cas1–Cas2 integrase complex.
- The Journal of Biological Chemistry also brings news about the structure and function of another CRISPR system. This is the Cas5c protein involved in the processing of long CRISPR RNA transcripts in Type I-C and Type II-A systems. The study reveals the functional diversity of Cas5c ribonucleases and provides further insight into the molecular mechanisms of substrate selectivity and activity of these enzymes.
- Beam Therapeutics announced new preclinical data on efforts to use base editors to treat chronic hepatitis B (HBV) infection. Cytosine base editors target and silence the viral covalently closed circular DNA (cccDNA), reducing HBV replication. Experimentally, base editing prevented HBV rebound in long-term infected primary hepatocytes.
- Acrigen Biosciences - a spin-off from the University of California, Berkeley - has raised an undisclosed amount of seed financing from Red Tree Venture Capital and others. Acrigen's mission is to advance and transform precision gene-editing technology to produce effective and safe in vivo drug therapies to cure disease.
- During the pandemic, we have seen the emergence of a wealth of novel point-of-care tests to detect SARS-CoV-2. Many are based on lateral flow immunoassays or advanced techniques, such as CRISPR-Cas9 and surface-enhanced Raman spectroscopy. In this review by researchers from Taiwan, the diagnostic sensitivity and specificity of the various commercial tests are outlined and compared.
- One of the lesser-known CRISPR-Cas systems - Class I, Type III-A - is a multi-component system employing Cas10. However, it has not been used for viral detection until now. A team of American researchers has developed a SARS-CoV-2 detection method based on an in vivo-reconstituted Type III-A CRISPR-Cas system. The technique has a sensitivity of 2000 copies/μl and 60 copies/μl, respectively, with and without isothermal amplification within 30 min.
- The genetic causes of muscular dystrophies are well characterized, and the CRISPR-Cas system for genome editing has opened a new path for disease treatment. This review by Eric Olson and co-workers discusses the challenges for translating CRISPR-Cas genome editing to a viable therapy for the permanent correction of muscular dystrophies.
- A review by researchers from India details the use of CRISPR-Cas9 in cancer immunotherapy. It gives a thorough introduction to most related fields, including the CRISPR-Cas system, repair mechanisms, the nature of cancer cells, oncogenes and chimeric antigen receptor T-cells.
- CRISPR-based functional genomics technologies that generate gene knockouts and single nucleotide variants have provided new essential insights into the function of homologous recombination (HR) genes. This review focuses on the response to PARP inhibition in cells deficient for the HR genes BRCA1 and BRCA2.
- A review in the CRISPR Journal looks at the increasingly refined and diverse CRISPR toolkit for silencing or activating genes with spatial and temporal precision in human pluripotent stem cells and their downstream applications. The researchers from the UK also discuss newer methods to install edits efficiently with single-nucleotide resolution and describe pooled CRISPR screens as a powerful means of unbiased discovery of genes associated with a phenotype of interest.
Huh, heh, wow
- The world's first CRISPR gene-edited food has recently gone on sale in Japan in the form of a tomato packed with a likely increase in nutritional content. CRISPR has enabled the tomato variety, Sicilian Rouge High GABA, to reduce the breakdown of GABA, so the tomatoes have around five times as much GABA in them. GABA is the chief inhibitory neurotransmitter in the human central nervous system, and the tomatoes are expected to reduce blood pressure in consumers.
Acute Myeloid Leukemia, AML, (NCT05066165)
Transfusion Dependent Beta-Thalassaemia, TDT, (NCT04925206)
EdiGene (GuangZhou) Inc.
EdiGene (GuangZhou) Inc.
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CAR T for CD19+ hematological cancers, (NCT05037669)
University of Pennsylvania
University of Pennsylvania