CMN Weekly (10 February 2023) - Your Weekly CRISPR Medicine News
Some of the best links we picked up around the internet
By: Gorm Palmgren - Feb. 10, 2023
Top picks
Researchers in Denmark and the US have explored the potential of a novel system for genome editing in human cells based on CRISPR-MAD7 - an alternative and royalty-free CRISPR-Cas12a nuclease developed from Eubacterium rectale (ErCas12a). Using a high-throughput engineering approach, the authors identified crRNAs that allow for ≤95% non-homologous end joining (NHEJ) and 66% frameshift mutations in various genes. They observed the high-cleavage fidelity of MAD7, resulting in an undetectable off-target activity. Moreover, they obtained ≤85% chimeric antigen receptor (CAR) insertions in primary T cells, thus exceeding the baseline integration efficiencies of therapeutically relevant transgenes using currently available virus-free technologies.
Research
Chinese researchers have developed a rapid and portable hepatitis B virus (HBV) DNA detection assay for low-level viremia patients. The assay is based on CRISPR-Cas13a combined with recombinase-aided amplification (RAA) technology. The sensitivity, specificity, positive predictive agreement (PPA), and negative predictive agreement (NPA) values of dynamic plasma detection in patients on antiviral therapy were 100%, 92.15%, 93.75%, and 100%, respectively.
Ensoma reports that the Danish Business Authority has cleared its acquisition of Twelve Bio, according to Danish foreign direct investment laws. As a result, the Co-founder of Twelve Bio, Stefano Stella, has joined the leadership team at Ensoma as vice president of gene editing. Moreover, Guillermo Montoya, co-founder of Twelve Bio, and Shengdar Q. Tsai, a member of the scientific advisory board of Twelve Bio, will join the scientific advisory board at Ensoma.
The first patient has been dosed in the phase 1 trial of Century Therapeutics gene-edited therapeutic CNTY-101 for relapsed or refractory CD19 positive B-cell lymphomas. CNTY-101 is an allogeneic cell therapy product candidate with six genetic modifications incorporated using sequential rounds of CRISPR. The modifications include a CD19-CAR, Allo-Evasion™ technology, IL-15 cytokine support and a safety switch.
Advances in gene therapy hold promise for treating hereditary hearing loss. The review addresses three main gene therapy strategies - gene replacement, gene suppression, and gene editing, summarising which approach is most appropriate for particular monogenic diseases based on different pathogenic mechanisms and then focusing on their successful applications for HHL in preclinical trials. Finally, it elaborates on the challenges and outlooks of gene therapy for HHL.
CRISPR/Cas genome editing in triple negative breast cancer: Current situation and future directions. The review focuses on summarising the molecular subtypes of TNBC, the CRISPR system and its potential applications in TNBC treatment. Moreover, it discusses several emerging strategies for utilising the CRISPR-Cas system to aid in the precise diagnosis of TNBC and the limitations of the CRISPR-Cas system.
Reversing the Central Dogma: RNA-guided control of DNA in epigenetics and genome editing. This review by researchers from Stanford University discusses how the normal flow of genetic information from DNA to RNA can be reversed by long noncoding RNAs (lncRNAs) and CRISPR, so the flow goes from RNA to DNA. The authors explore the parallels between these two fields and highlight opportunities for synergy and future breakthroughs.
On Monday, we brought a clinical roundup on gene-edited CAR T therapies. The roundup summarises the clinical-stage gene-edited CAR T candidates for cancer and looks at some of the significant edits they feature.