Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
OMEGA RNA (ωRNA)-guided endonuclease IscB, the evolutionary ancestor of Cas9, is an attractive system for in vivo genome editing because of its compact size and mechanistic resemblance to Cas9. However, wild-type IscB-ωRNA systems show limited activity in human cells. Here we report enhanced OgeuIscB, which, with eight amino acid substitutions, displayed a fourfold increase in in vitro DNA-binding affinity and a 30.4-fold improvement in insertion-deletion (indel) formation efficiency in human cells. Paired with structure-guided ωRNA engineering, the enhanced OgeuIscB-ωRNA systems efficiently edited the human genome across 26 target sites, attaining up to 87.3% indel and 62.2% base-editing frequencies. Both wild-type and engineered OgeuIscB-ωRNA showed moderate fidelity in editing the human genome, with off-target profiles revealing key determinants of target selection including an NARR target-adjacent motif (TAM) and the TAM-proximal 14 nucleotides in the R-loop. Collectively, our engineered OgeuIscB-ωRNA systems are programmable, potent and sufficiently specific for human genome editing.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213078 | PMC |
| http://dx.doi.org/10.1038/s41589-024-01669-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The X-Age Project to construct a Chinese aging clock.
Nat Aging
September 2025
Aging Biomarker Consortium (ABC), Beijing, China.
The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age-related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual's physiological and molecular state, across diverse Chinese cohorts.
View Article and Find Full Text PDFPPR596 Is Required for nad2 mRNA Splicing and Complex I Biogenesis in Mitochondria of Arabidopsis thaliana.
Physiol Plant
September 2025
Department of Plant Physiology, Institute of Biology, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
Several genes in the mitochondria of angiosperms are interrupted by introns, and their posttranscriptional excision involves numerous nucleus-encoded auxiliary factors. Most of these factors are of eukaryotic origin, among them members of the pentatricopeptide-repeat (PPR) family of RNA-binding proteins. This family divides into the PLS and P classes, with PLS-class proteins typically participating in C-to-U mRNA editing and P-class members contributing to transcript stabilization and intron splicing.
View Article and Find Full Text PDFWhy transport matters: an update on carrier proteins in Apicomplexan parasites.
Curr Opin Microbiol
September 2025
Cryptosporidiosis Laboratory, The Francis Crick Institute, London, United Kingdom. Electronic address:
The movement of molecules across the membranous barriers of a cell is fundamental to cellular homeostasis in every living organism. This vital process is facilitated through a mechanistically diverse class of proteins, collectively known as membrane transporters. Among these are so-called carrier proteins that can function in passive and active transport mechanisms.
View Article and Find Full Text PDFWheat-related allergic reactions: causes of prevalence differences and allergenicity reduction methods review.
Crit Rev Food Sci Nutr
September 2025
Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University (BTBU), Beijing, China.
Wheat, a significant source of protein, can also induce various wheat-related allergic reactions (WRARs). Statistical data show significant spatiotemporal and geographical variations in the prevalence of WRARs. Studies reveal that hexaploid wheat exhibits notably higher allergenicity.
View Article and Find Full Text PDFift140-Deficient Zebrafish as a Model for Kidney Cystogenesis and an F0-Based Screen for Genetic Modifiers of Kidney Cysts.
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.