Programmable nucleases are cutting edge genetic technology which edits targeted DNA sequences through generation of site-specific double-strand DNA breaks (DSBs). To improve the efficiency and precision of genetic modification, scientists have developed a single-base editing system (base editor) through combining of CRISPR/Cas9 system with cytosine deaminase. Compared with Cas9 system, this base editor can convert cytosine to thymine (C > T) at specific site more efficiently without inducing DSBs to avoid generation of indels. However, the base editor can only generate transition of pyrimidine but could not modify purines. Recently, Nature published a novel base editing system to convert adenine to guanine (ABEs, adenine base editors) through fusion of Cas9 nickase to a modified deaminase which is evolved through screening of random library based on tRNA adenine deaminase from E. coli. Here, we summarize the development of single-base editing tools and the latest research progress, especially the optimization process of ABEs, as well as the potential directions of the base editors.
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http://dx.doi.org/10.16288/j.yczz.17-389 | DOI Listing |
Vet Microbiol
March 2025
Department of Animal Science and Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, United States. Electronic address:
CD163 is the primary receptor for PRRSV, and its SRCR5 domain, encoded by exon 7, is crucial for supporting PRRSV infection. Previous studies have used CRISPR/Cas9 technology to remove exon 7 from the host genome, and the edited pigs were completely resistant to PRRSV infection. In this study, we used CRISPR/Cas9 technology mimicking an adenine base editor (ABE) to edit the splice acceptor site of exon 7, rendering it nonfunctional.
View Article and Find Full Text PDFAdv Mater
March 2025
Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 1UL, UK.
Base editing, a CRISPR-based genome editing technology, enables precise correction of single-nucleotide variants, promising resolutive treatment for monogenic genetic disorders like recessive dystrophic epidermolysis bullosa (RDEB). However, the application of base editors in cell manufacturing is hindered by inconsistent efficiency and high costs, contributed by suboptimal delivery methods. Nanoneedles have emerged as an effective delivery approach, enabling highly efficient, non-perturbing gene therapies both in vitro and in vivo.
View Article and Find Full Text PDFFront Pharmacol
February 2025
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität, Berlin, Germany.
Objective: Intestinal current measurement (ICM) provides a sensitive bioassay for assessment of cystic fibrosis transmembrane conductance regulator (CFTR) function in rectal biopsies and is used as a diagnostic tool for cystic fibrosis (CF). Furthermore, ICM was shown to be sensitive to detect pharmacological rescue of CFTR function by CFTR modulators in people with CF carrying responsive mutations. Results from clinical trials of CFTR modulators across age groups indicate that CFTR function in the sweat duct may be age-dependent with children reaching higher levels than adults.
View Article and Find Full Text PDFAppl Environ Microbiol
March 2025
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
Intestinal microbiota members of the genus are increasingly explored as probiotics and therapeutics. However, the paucity of genetic tools and the widespread restriction modification (RM) systems in limit our ability to genetically manipulate these bacteria. Here we established a CRISPR-Cas9 cytosine base editor system (cBEST) for portable genome editing in bifidobacteria.
View Article and Find Full Text PDFSmart Med
March 2025
Joint Centre of Translational Medicine, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine The First Affiliated Hospital of Wenzhou Medical University Wenzhou China.
Wound healing has been a continuous critical focus in clinical practice, posing the ongoing challenges and burdens to patients. Current attempts tend to develop multi-drug loaded patches with spatial design. Herein, we present a multifunctional microneedle patch that integrates different drugs into separated regions for wound treatment.
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