Three new CRISPR gene editing systems that perform better than Cas9 are characterised by scientists at Metagenomi, California. The new CRISPR effector nucleases belong to type II (MG3-6 and a chimeric version MG3-6/4) and type V (MG29-1) and were sourced from the human microbiome and a hydrothermal vent, respectively. The authors find that all three systems can perform reproducible, high-frequency gene editing. e.g., disruption of the T cell receptor (TCR) alpha-chain was induced in >95% of cells, both paralogues of the TCR beta-chain in >90% of cells, and >90% knockout of β2-microglobulin, TIGIT, FAS, and PDCD1.
A new TALEN-based method enables efficient strand-selective base editing of human mitochondrial DNA. CRISPR-based strategies are hampered by the difficulty of delivering guide RNAs into mitochondria, while DNA binding in TALEN relies on highly variable amino acid sequences without additional guides. Circular RNAs encoding the mitoBEs delivered the tools into patient-derived cells, enabling up to 77% base-editing efficiency and high specificity in various pathogenic mitochondrial DNA mutations.
American scientists demonstrate CRISPR-based engineering of RNA viruses in a not-yet peer-reviewed paper. The authors combined sequence-specific VRISPR-based RNA cleavage with programmable RNA repair to make precise deletions and insertions in RNA. Approximately 5% of the bulk virus could be edited as intended.
A new versatile and efficient approach for precisely integrating large, gene-sized DNA fragments - LOCK - utilises specially designed 3'-overhang double-stranded DNA (odsDNA) donors harbouring 50-nt homology arm. LOCK allows highly efficient targeted insertion of kilobase-sized DNA fragments into the mammalian genomes with low cost and low off-target effects, yielding >fivefold higher knock-in frequencies than conventional homologous recombination-based approaches.
The applications of CRISPR/Cas-mediated genome editing in genetic hearing loss. This review details the recent achievements of the CRISPR-Cas technique in disease modelling and therapeutic strategies for congenital hearing loss. Furthermore, it discusses the challenges of applying CRISPR-Cas techniques in future clinical treatments.
A review on CRISPR/Cas: a versatile tool for cancer screening, diagnosis, and clinic treatment. This review discusses various CRISPR-Cas-derived genome and epigenome tools for cancer biology study and treatment and their efficiency and long term-safety. It also looks at developing new CRISPR-Cas delivery methods and reducing potential side effects, including off-target impacts in cancer-related research, diagnosis, and therapeutical treatment.