CMN Weekly (24 June 2022) - Your Weekly CRISPR Medicine News
By: Gorm Palmgren - Jun. 24, 2022
Top picks
- CRISPR-Cas12a knockout of microRNA-21 (miR-21) reduces glioma growth in mice in vitro and in vivo. Researchers in the Netherlands disrupted the coding sequences of miR-21, which is a significant driver of glioma growth. The intervention resulted in the upregulation of many downstream miR-21 target mRNAs involved in proliferation. Phenotypically, CRISPR-edited glioma cells showed reduced migration, invasion and proliferation.
- Swiss researchers have shown that catalytically dead Cas9 (dCas9) without gRNAs non-specifically affects gene expression in human-induced pluripotent stem cells (hiPSCs). Transcriptomics analysis revealed that a significant number of genes involved in developmental processes and various other genes with non-overlapping biological functions are affected by dCas9 overexpression. The effect is specific to the condition when cells are cultured in a medium that does not actively maintain the pluripotency network.
Research
- Researchers in Belgium have optimised and validated a non-viral genetic modification platform to inactivate allogeneic T cell receptors (TCRs) for CAR T cell therapies. The method is based on Sleeping Beauty transposons delivered with minicircles to express CD19-28z.CAR and CRISPR-Cas9 ribonucleoparticles.
- Japanese researchers have prepared 4′-thio-modified gRNAs that are chemically protected from intracellular degradation. The approach is described as a simple way to obtain chemically modified RNA suitable for CRISPR-Cas9 gene editing.
- Chinese researchers have developed a DNA origami-based single-molecule CRISPR machine that can perform spatially resolved DNA cleavage via two different searching modes. The free searching mode leads to searching activity that gradually decays with the distance, whereas the localised mode generates spatially-confined searching activity.
- In a not yet peer-reviewed publication, Jennifer Doudna and co-workers have shown that the CRISPR-Csm complex - a multi-protein effector from type III CRISPR immune systems in prokaryotes - provides surgical RNA ablation of both nuclear and cytoplasmic transcripts. Furthermore, CRISPR-Csm uses a programmable RNA-guided mechanism to find and degrade target RNA molecules without inducing indiscriminate trans-cleavage of cellular RNAs. As a result, high-efficiency RNA knockdown (90-99%) and minimal off-target effects were achieved in human cells.
Industry
- Precision BioSciences and Novartis have entered an exclusive worldwide in vivo gene editing research and development collaboration and license agreement. As part of the agreement, Precision will develop a custom ARCUS nuclease that will be designed to insert, in vivo, a therapeutic transgene at a "safe harbour" location in the genome. The aim is to develop potential one-time transformative treatment options for diseases including certain hemoglobinopathies such as sickle cell disease and beta-thalassemia.
- Precision BioSciences also announced a $50 million offering of common stock that will all be sold by the company. Precision BioSciences intends to use the net proceeds of the offering to help fund ongoing and planned research and development and for working capital and general corporate purposes.
Detection
- Chinese researchers have developed an ultrasensitive and visual in-one-tube detection method for SARS-CoV-2. The technique involves nucleic acid enrichment with magnetic beads, amplification by RT-PCR, CRISPR-Cas12a mediated trans cleavage and fluorescence signal detection.
- Other researchers in China describe a new photo-controlled CRISPR-based method for the clinical detection of SARS-CoV-2 RNA. The procedure is based on optochemical control of CRISPR RNA (crRNA) activation, recombinase polymerase amplification (RPA) and CRISPR-Cas12a detection, and the system can be integrated into a completely closed test tube.
- Yet another Chinese method for SARS-CoV-2 detection relies on CRISPR-Cas13a cascade technology. Cas13a-crRNA was utilised to recognise the viral target RNA directly, and the recognition events sequentially initiate the transcription amplification to produce light-up RNA aptamers for output fluorescence signal.
Reviews
- A review by researchers in Iran looks into CRISPR-Cas9 gene editing as a new approach for overcoming drug resistance in cancer. Studies related to the applications of gene editing in overcoming drug resistance in cancer cells are reviewed, and a brief overview of the limitations of the technique is presented.
- A review by researchers in Portugal gives a general introduction to CRISPR. It explains the functioning and the advantages that this technique may have compared to previously developed methods, such as RNA interference (RNAi), Zinc Finger Nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs).
- Researchers in Singapore present a medicinal chemist’s perspective on small-molecule enhancers of CRISPR-induced homology-directed repair (HDR) in gene therapy. The review discusses the relatively low efficiency of the HDR pathway compared with the rival random repair pathway, non-homologous end joining (NHEJ). Furthermore, it outlines how small molecules can be employed to increase the efficiency of HDR and decrease that of NHEJ.
News from CRISPR Medicine News
- On Wednesday, we brought a clinical trial update about positive results for gene-edited therapies for cancer and blood disease. The updates include positive data from Caribou Biosciences' ongoing trial for CB-010 in B cell non-Hodgkin lymphoma, positive data for CRISPR Therapeutics' CTX130 in relapsed or refractory T cell malignancies, and long-time positive data for CRISPR Therapeutics' and Vertex Pharmaceuticals jointly-developed exa-cel (CTX001) for beta-thalassemia and sickle cell disease.
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Tags
CLINICAL TRIALS
IND Enabling
Phase I
Phase II
Phase III
IND Enabling
Phase I
Phase II
Phase III
Amyotrophic Lateral Sclerosis, ALS, or Frontotemporal Dementia FTD, (NCT04931862)
Sponsors:
Wave Life Sciences Ltd.
Sponsors:
Wave Life Sciences Ltd.
IND Enabling
Phase I
Phase II
Phase III