CMN Weekly (18 February 2022) - Your Weekly CRISPR Medicine News
By: Gorm Palmgren - Feb. 18, 2022
- The use of Type III CRISPR-based RNA editing for programmable control of SARS-CoV-2 is presented by researchers in the USA and China. The method, TEAR-CoV, leads to RNA-guided coronavirus transcript degradation both in vitro and in eukaryotic cells. Bioinformatics screening of gRNAs along RNA sequences reveals that a group of five gRNAs could potentially target 99.98% of human coronaviruses.
- A new approach for the knock-in of long sequences in mammalian cells is proposed by American researchers. The method couples microbial single-strand annealing proteins (SSAPs) with catalytically inactive dCas9 for cleavage-free gene-editing. The authors demonstrate efficiencies of up to 20% and robust performance across donor designs and cell types, including human stem cells.
- Researchers in Japan have studied gRNA features in CRISPR-Cas9 ribonucleoprotein (RNP) complexes with dual-guide RNAs (dgRNAs) composed of crRNA and tracrRNA. The study, which was performed in zebrafish, identified novel position-specific mononucleotide features with confirmed cleavage efficiencies throughout the protospacer sequence. The study also identified specific differences between wild-type Cas9 and HiFi Cas9.
- Another Japanese research team has used CRISPR-Cas9 and single-stranded oligodeoxynucleotides (ssODNs) for the complete deletion of the full-length NPHP1 gene in human induced pluripotent stem cells (iPSCs). Mutations in NPHP1 cause familial juvenile nephronophthisis and the new method could be useful for the analysis of genetic disorders that are difficult to reproduce by conventional knockout methods.
- An international research team has used CRISPR base editing to identify novel mutations in the HBG promoter that elevate the expression of fetal haemoglobin. Base editing at -123 and -124bp of the HBG promoter induced HbF to a higher level than disruption of well-known BCL11A binding site in erythroblasts, suggesting a therapeutic strategy for patients with hereditary persistence of fetal haemoglobin.
- American researchers have developed a new open-source tool, CROPSR, for automated genome-wide design and evaluation of gRNA sequences for CRISPR experiments. CROPSR is particularly useful for complex, repetitive and polyploid crop genomes, but also delivers a significant increase in prediction accuracy over existing tools in non-crop genomes.
- CD81 has been associated with the development of human cancers. Now, researchers from Iran demonstrate the introduction of targeted mutations in the CD81 gene of the MDA-MB-231 breast cancer cell line using a plasmid-based CRISPR-Cas9 system.
- A targeted delivery system for effective genome editing of CXCR4 in acute myeloid leukaemia (AML) cells are presented by Chinese researchers. The system employs a dual-targeting nanosystem composed of MUC1 specific aptamer incorporated alginate and T22-NLS peptide with T22 sequence targeting CXCR4. Results showed that the genome editing nanosystem can effectively knock out CXCR4 in leukaemia cells.
- Synthego has raised $200 million of growth capital in a Series E financing. The financing will be used to further develop its Halo and Eclipse platforms and its next-generation technology CRISPROff. The company also announced that it recently appointed Avi Raval as chief financial officer. Mr Raval comes from a position as a managing director and founding member of the health care group at Perella Weinberg Partners.
- Intellia and ONK Therapeutics have announced a licensing and collaboration agreement to advance allogeneic CRISPR-edited NK cell therapies for the treatment of patients with cancer. In the agreement, ONK will have non-exclusive rights to Intellia's ex vivo genome editing and LNP delivery technologies and exclusive rights to certain guide RNAs for up to five allogeneic CRISPR-edited NK cell therapies. Intellia will in return receive global co-development and co-commercialization options for up to two CRISPR-edited NK cell therapies with lead commercialization rights in the U.S.
- CRISPR Therapeutics has reported a net income of $377.7 million for the full year 2021 and a cash position of $2,379.1 million. In a business update, the company reports that more than 70 patients have now been dosed with CTX001 for the treatment of beta-thalassemia and sickle-cell disease, that the first patient has been dosed with VCTX210 for the treatment of type 1 diabetes, and that other clinical trials are progressing.
- Business Insider has published a narrative by Andrew Dunn about Shakked Halperin, CEO of Rewrite Therapeutics that was recently sold to Intellia Therapeutics for $45 million cash and an additional $155 million in milestones. Halperin founded the company in 2020 and raised just $2 million before selling it for potentially 100 times as much.
- A CRISPR-Cas-based method for colourimetric detection of prostate-specific antigen (PSA) in serum samples is presented by Chinese researchers. The method employs nicking enzyme-free strand displacement ampliﬁcation that is activated by PSA and generates amplicons that can be recognized by the CRISPR-Cas12a system.
- Researchers in China present a dual-aptamer-regulated CRISPR-Cas12a system for dynamic monitoring of viral myocarditis injury. The nature-inspired 3D photonic crystal interface-coated biochip utilises an energy-confined upconversion nanoparticle to boost the luminescence 27-fold.
- The employment of Cas12 and Cas13 in CRISPR-based disease diagnosis is the subject of a review by Indian researchers. The review discusses various advancements and the potential shortfalls and challenges in the widespread adaptation of this technology for SARS-CoV-2 and beyond.
- A Chinese review discusses advances in CRISPR-Cas based amplification-free detection of nucleic acids. The review looks into various signal enhancement strategies and presents the pros and cons of detection systems with and without amplification.
- A review of the use of new CRISPR tools in cardiovascular research and medicine is presented in Nature Reviews Cardiology by researchers from Stanford University School of Medicine. Among other topics, the authors discuss the prospect of therapeutic genome editing by CRISPR tools to cure genetic cardiovascular diseases.
- A German review takes a look at the therapeutic applications of CRISPR-activation (CRISPRa) that are based on programmable recruitment of transcription factors to specific loci and subsequent activation of genes. The review discusses the currently available CRISPRa modules, recent developments, and future potentials and limitations of this approach with a focus on therapeutic applications and in vivo delivery.
- A systematic review by researchers from Taiwan identifies new approaches to increase CRISPR-editing efficiencies in stem cell transplantation for HIV treatment. The review discusses proposed methods for double gene knockout and knockout-knockin, ribonucleoprotein and Adeno-associated virus delivery, and the choice between SpCas9 and SaCas9.
- Recent CRISPR-Cas9 strategies to restore dystrophin expression in vitro and in animal models of Duchenne muscular dystrophy is presented in a review by researchers from Canada.
- Indian researchers review the role of the CRISPR-Cas system in cancer drug development and its application to biomarker identification and validation, high-end target genes, and breakthrough anti-cancer cell therapies. The authors also highlight the role of CRISPR-Cas in precision disease modelling and functional drug screening.
Meetings and webinars
- The 4th CRISPR in Drug Discovery: From Targets to Therapeutics meeting will be held face to face in Cambridge, UK, 1-2 March. The meeting will focus on the application of genome engineering in the identification of novel drug targets through large scale CRISPR based functional genomics studies and developing advanced cellular and in vivo disease models for target validation.
- "CRISPR goes viral: Biology and applications of a bacterial immune system" is the title of a webinar by Professor John van der Oost of Wageningen University that will air on 17 March at 3 pm GMT.
News from CRISPR Medicine News
- The state of play in the field of CRISPR diagnostics has been changing rapidly. Here, Bryan DeChairo, CEO of Sherlock Biosciences, discusses the progress, challenges, and future of CRISPR diagnostics for COVID-19 and beyond.
- In this week's clinical trial update, we summarise the ongoing in vivo CRISPR clinical trials for three distinct rare genetic diseases: hereditary transthyretin amyloidosis, Leber congenital amaurosis 10, and hereditary angioedema.
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Solid Tumors (NCT03970382)
PACT Pharma, Inc.
PACT Pharma, Inc.
Beta-Thalassemia, BT, (NCT05442346)
View all clinical trials
Sickle Cell Disease, SCD, and Transfusion Dependent Beta-Thalassaemia, TDT, (NCT04208529)
Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated