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| http://dx.doi.org/10.1016/j.xjtc.2023.02.008 | DOI Listing |
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Herbicide-resistant plants produced by precision adenine base editing in plastid DNA.
Nat Plants
November 2024
GreenGene, Inc., Seoul, Republic of Korea.
CRISPR-free, protein-only cytosine base editors (CBEs) or adenine base editors, composed of DNA-binding proteins such as zinc finger proteins or transcription activator-like effectors (TALEs) and nucleobase cytosine or adenine deaminases, respectively, enable organellar DNA editing in cultured cells, animals and plants. TALE-linked double-stranded DNA deaminase toxin A (DddA)-derived CBEs (DdCBEs) and TALE-linked adenine deaminases (TALEDs) install C-to-T and A-to-G single-nucleotide conversions, respectively, in mitochondria and chloroplasts. Interestingly, whereas TALEDs exclusively induce A-to-G conversions without C-to-T conversions in mammalian mitochondrial DNA, they often install unwanted C-to-T edits in addition to intended A-to-G edits in plastid DNA.
View Article and Find Full Text PDFUnconstrained Precision Mitochondrial Genome Editing with αDdCBEs.
Hum Gene Ther
October 2024
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
DddA-derived cytosine base editors (DdCBEs) enable the targeted introduction of C•G-to-T•A conversions in mitochondrial DNA (mtDNA). DdCBEs work in pairs, with each arm composed of a transcription activator-like effector (TALE), a split double-stranded DNA deaminase half, and a uracil glycosylase inhibitor. This pioneering technology has helped improve our understanding of cellular processes involving mtDNA and has paved the way for the development of models and therapies for genetic disorders caused by pathogenic mtDNA variants.
View Article and Find Full Text PDFPhage-Mediated Digestive Decolonization in a Gut-On-A-Chip Model: A Tale of Gut-Specific Bacterial Prosperity.
Viruses
June 2024
Institute of Experimental and Clinical Research, Pediatric Department (IREC/PEDI), Université Catholique de Louvain-UCLouvain, 1200 Brussels, Belgium.
Infections due to antimicrobial-resistant bacteria have become a major threat to global health. Some patients may carry resistant bacteria in their gut microbiota. Specific risk factors may trigger the conversion of these carriages into infections in hospitalized patients.
View Article and Find Full Text PDFImprovement of TaC9-ABE mediated correction of human SMN2 gene.
Biotechnol Bioeng
October 2024
Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine, Wuyi University, Jiangmen, China.
Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Gene editing technology repairs the conversion of the 6th base T to C in exon 7 of the paralogous SMN2 gene, compensating for the SMN protein expression and promoting the survival and function of motor neurons. However, low editing efficiency and unintended off-target effects limit the application of this technology.
View Article and Find Full Text PDFComprehensive analysis of the editing window of C-to-T TALE base editors.
Sci Rep
June 2024
Cellectis Inc, New York, NY, USA.
One of the most recent advances in the genome editing field has been the addition of "TALE Base Editors", an innovative platform for cell therapy that relies on the deamination of cytidines within double strand DNA, leading to the formation of an uracil (U) intermediate. These molecular tools are fusions of transcription activator-like effector domains (TALE) for specific DNA sequence binding, split-DddA deaminase halves that will, upon catalytic domain reconstitution, initiate the conversion of a cytosine (C) to a thymine (T), and an uracil glycosylase inhibitor (UGI). We developed a high throughput screening strategy capable to probe key editing parameters in a precisely defined genomic context in cellulo, excluding or minimizing biases arising from different microenvironmental and/or epigenetic contexts.
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