CMN Weekly (9 December 2022) - Your Weekly CRISPR Medicine News
By: Gorm Palmgren - Dec. 9, 2022
- Jennifer Doudna and colleagues describe a simple strategy to influence DNA repair pathway choice and improve HDR efficiency by decorating chromatin with engineered CRISPR-Cas9-methyltransferase fusion proteins. This strategy highlights the impact of histone modifications on DNA repair following CRISPR-Cas-induced double-stranded breaks and adds to the CRISPR genome editing toolbox.
- South China Morning Post reports that He Jiankui - the Chinese scientist behind gene-edited babies - will discuss the ethics of his research in a series of public talks in March at Oxford University. He was released from prison earlier this year and is now looking at how CRISPR technology can help treat genetic diseases.
- British researchers have investigated how primary chromatin structure and epigenetics may influence off-target activity in CRISPR-Cas9 genome editing. They publish an off-target dataset containing 19 epigenetic features. The authors believe it will help the CRISPR-Cas9 community understand the relationship between epigenetic markers and CRISPR-Cas9 off-target activity.
- Researchers in Denmark have developed a method for multiparametric and accurate functional analysis of genetic sequence variants using CRISPR-Select. It is a set of flexible knock-in assays that introduce a genetic variant in a cell population and track its absolute frequencies relative to an internal, neutral control mutation as a function of time, space or a cell state measurable by flow cytometry.
- American researchers have explored the feasibility of adenine base editing (ABE)-mediated exon skipping as a therapeutic strategy for Duchenne muscular dystrophy (DMD). In a DMD hiPSC cell model, they demonstrated that transfection of an ABE and a gRNA targeting the splice acceptor led to efficient conversion of AG to GG (35.9 ± 5.7%) and enabled exon 55 skipping. Furthermore, complete AG to GG conversion in a single clone restored dystrophin expression (42.5 ± 11.0% of WT).
- Preliminary results from Vor Biopharma reported that the first patient given its gene editing therapy for acute myeloid leukaemia (AML) is in remission. The medication is called trem-cel (formerly VOR33) and uses CRISPR-Cas9 in blood cells to knock out CD33, thereby making them resistant to the CD33-targeted therapy Mylotarg.
- Editas Medicine announced positive initial clinical data from the first two patients with sickle cell disease (SCD) treated with EDIT-301 in the Phase 1/2 RUBY trial. EDIT-301 uses AsCas12a, a novel, proprietary, highly efficient, and specific gene editing nuclease, to edit the promoter regions of gamma-globin gene 1 and 2 to increase the expression of HbF to mimic the natural mechanism of hereditary persistence of fetal haemoglobin to treat SCD.
- Poseida Therapeutics presented early clinical results from its Phase 1 clinical trials of P-MUC1C-ALLO1 and P-BCMA-ALLO1 - two gene-edited allogeneic cell therapies for solid tumours and relapsed/refractory multiple myeloma, respectively - at the recent ESMO I-O 2022 Annual Congress.
- Beam Therapeutics announced that FDA had lifted the clinical hold on its IND application for BEAM-201. The multiplex base-edited T-cell therapy BEAM-201 has been developed to treat relapsed/refractory T-cell acute lymphoblastic leukaemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LL).
- A novel ultrasensitive sensor for detecting microRNAs is based on CRISPR-Cas12a and click chemistry-terminal deoxynucleotidyl transferase (ccTdT) for signal amplification. The sensor has a broad linear detection range, from 1 pM to 105 pM, with detection limits as low as 88 fM under optimal experimental conditions.
- Monkeypox virus can now be detected with the naked eye with a portable CRISPR-Cas-based system. The system harnesses the high selectivity of CRISPR-Cas12 and the isothermal nucleic acid amplification potential of recombinase polymerase amplification (RPA).
- Chinese researchers have developed a one-step CRISPR-Cas12a-mediated isothermal amplification for rapid and high-resolution digital detection of rare mutant alleles. CRISPR ASsoaciated Mutation Allele Rapid Test (CASMART) is an alternative to conventional single nucleotide polymorphism detection methods.
- Chinese researchers report on a method for the rapid and unamplified detection of SARS-CoV-2 RNA via CRISPR-Cas13a-modified solution-gated graphene transistors. Using the gene-targeting capacity of CRISPR-Cas13a and gate functionalization via multilayer modification, SARS-CoV-2 nucleic acid sequences can be quickly and precisely identified without the need for amplification or fluorescence tagging.
- Taiwan researchers look at nanoparticle-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases. The review highlights important advances in nanoparticle-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids focusing on IRDs.
- A review by Chinese researchers highlights the recent development of CRISPR/Cas-based biosensors for miRNA detection. We summarize these miRNA biosensors' principles, features, and performance and highlight the remaining challenges and future directions.
- A Pakistan researchers review discusses the genome editing strategies and potential applications of prime editing for treating β-thalassemia. In addition, the review also focuses on challenges associated with the use of prime editing.
News from CRISPR Medicine News
- This week's clinical update looked at the latest clinical data from Editas Medicine's ongoing RUBY trial for EDIT-301 in severe sickle cell disease. It also brought updates about Caribou Biosciences' PD-1 knockout CAR-T cell therapeutic candidate for relapsed or refractory large B cell lymphoma and non-Hodgkin lymphoma.
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Epithelial Ovarian Cancer, (EOC), NCT05617755
Arsenal Biosciences, Inc.
Arsenal Biosciences, Inc.
Hemophilia B & Mucopolysaccharidosis, MPS, (NCT04628871)
View all clinical trials
Duchenne Muscular Dystrophy, DMD, (NCT05514249)
Cure Rare Disease, Inc
Cure Rare Disease, Inc