CRISPR-Cas systems articles from across Nature Portfolio

Single-cell CRISPR screening is a powerful method for biological discovery. Such screens genetically perturb many genes in parallel and use single-cell RNA sequencing to assess the transcriptomic effects. Now, an in vivo protocol facilitates screens in mouse brain, using adeno-associated virus with transposon-based delivery of the CRISPR guide RNAs.

Genetic interaction (GI) mapping is a powerful approach to identify functional genetic dependencies. Here, the authors explore RNA-targeting Cas13d for GI mapping. They discover and overcome gRNA interference and optimize knockdown efficiency, paving the way for quantitative GI studies with Cas13d.

The mechanisms underlying optimal transcriptional activation remain elusive. Here, the authors show that CRISPR-SunTag activators form liquid-like droplets and boost gene expression, while increased SunTag scaffolds creates solid-like condensates that sequester coactivators, impairing activation.

Prime editing systems (PEs) hold great promise though the editing range is limited to downstream sequences of the pegRNA nick. Here, the authors report the extended prime editor system (EXPERT), which overcomes this limitation enabling efficient editing on both sides of the pegRNA nick.

Obesity, a surging global health challenge, needs effective and innovative therapeutic models. Here, the authors show in mice a microneedle drug delivery platform loaded with metal-organic frameworks (MOFs) and CRISPRa-UCP1 system to enable sono-gene therapy for obesity.

CRISPR-Cas13 mediated editing of RNA corrects a common mutation in the retinal degeneration gene USH2A, and restores usherin expression in mouse photoreceptors when delivered with adeno-associated viral gene therapy.

SeqCas9, a Cas9 variant from the Streptococcus family, recognizes a simple NNG PAM with high activity and enhanced specificity, highlighting its potential as an efficient and precise tool for gene editing applications.

Single-cell CRISPR screening is a powerful method for biological discovery. Such screens genetically perturb many genes in parallel and use single-cell RNA sequencing to assess the transcriptomic effects. Now, an in vivo protocol facilitates screens in mouse brain, using adeno-associated virus with transposon-based delivery of the CRISPR guide RNAs.

Optimized methods for the synthesis of circular RNA in vitro and in cells, and a complementary Cas9 de-immunization method, enhance RNA persistence and reduce immunogenicity for applications in genome engineering and cell engineering.

CRISPR screens in cell cultures reveal cancer dependencies yet often miss the metabolic nuances of tissues. In this Comment, Zuber and Palm highlight how modelling tumour-specific metabolic conditions can enhance our understanding of cancer biology and improve therapeutic discovery.

The nuclease Cas9 and DNA-repair pathway homology-mediated end joining can be leveraged to efficiently and non-virally integrate large DNA payloads into genomic target sites in primary T cells.

Base editing can correct the hearing-loss phenotype in mice harbouring a common mutation in the otoferlin gene.