Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA895214 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Functional correction of the CFTR 1717-1G>A mutation using a precise adenine base editor
| PRJNA1209370 | ENA
Project description:We then deliver the ‘RESTART v3’ system, which is a CRISPR-free RNA base editor for nonsense mutation suppression, into the cochlea of the mice. We achieve physiological otoferlin expression, the edited premature termination codon is reverse-mutated to the original amino acid. We observe significant hearing restoration and enhancement of the behavioral auditory startle reflex.
2025-10-31 | PXD070139 |
Project description:We used an adenine base editor to target the translation start site and mRNA splicing site of Camk2d in order to knock out CaMKIIδ. We found that editing the 5' splice site of intron 7 can lead to premature translation termination, effectively knocking out CaMKIIδ.
2025-01-21 | GSE266652 | GEO
Project description:We used an adenine base editor to target the translation start site and mRNA splicing site of Camk2d in order to knock out CaMKIIδ. We found that editing the 5' splice site of intron 7 can lead to premature translation termination, effectively knocking out CaMKIIδ.
2025-01-21 | GSE265935 | GEO
Project description:We evaluate CRISPR-based prime editing for application in organoids. First we model mutations in TP53 in intestinal and hepatocyte oganoids and determine the efficiency and accuracy of mutation induction on multiple targets. Then, to evaluate potential clinical applicability of prime editing we repair mutations in the CFTR channel that cause cystic fibrosis in intestinal organoids. First we repair the CFTR-F508del mutation which is the most common mutation in cystic fibrosis. Then we compare adenine base editing to prime editing by repairing the CFTR-R785* mutation using both strategies.
| EGAS00001005358 | EGA
Project description:Current base editors use DNA deaminases, including cytidine deaminase in cytidine base editor (CBE) or adenine deaminase in adenine base editor (ABE), to facilitate transition nucleotide substitutions. Combining CBE or ABE with glycosylase enzymes can induce limited transversion mutations. Nonetheless, a critical demand remains for base editors capable of generating alternative mutation types, such as T>G corrections. In this study, we leveraged pre-trained protein language models to optimize a uracil-N-glycosylase (UNG) variant with altered specificity for thymines (eTDG). Notably, after two rounds of testing fewer than 50 top-ranking variants, more than 50% exhibited over 1.5-fold enhancement in enzymatic activities. When eTDG was fused with nCas9, it induced programmable T-to-S (G/C) substitutions and corrected db/db diabetic mutation in mice (up to 55%). Our findings not only establish orthogonal strategies for developing novel base editors, but also demonstrate the capacities of protein language models for optimizing enzymes without extensive task-specific training data.
2024-01-23 | GSE253655 | GEO
Project description:Restrictive cardiomyopathy (RCM) is a severe cardiac disorder characterized by impaired ventricular filling and diastolic dysfunction, with mutations in sarcomeric proteins representing major causative factors. Mutations of TNNI3 gene (e.g. p.R192H) constitute major genetic causes of RCM, particularly affecting pediatric patients and being associated with poor prognosis. Here, we demonstrate that adenine base editor (ABE) is able effectively correct RCM-causing mutation and alleviate RCM in a murine model. We first developed a novel murine model harboring the Tnni3R193H mutation that recapitulates the hallmark features of human RCM. Importantly, targeted delivery of ABE via adeno-associated virus (AAV) achieved efficient and precise correction of the Tnni3R193H mutation in adult RCM mice, leading to significant improvement of cardiac functions. Our findings establish base editing as a therapeutic strategy for RCM and highlight its broader potential for treating genetic cardiomyopathies in clinical settings.
2025-04-30 | GSE295799 | GEO
Project description:The most common form of genetic heart disease is hypertrophic cardiomyopathy (HCM), which is caused by mutations in cardiac sarcomeric genes and leads to abnormal heart muscle thickening. Complications of HCM include heart failure, arrhythmia, and sudden cardiac death. The dominant-negative c.1208 G>A (p.R403Q) mutation in b-myosin (MYH7) is a common and well-studied mutation that leads to increased cardiac contractility and HCM onset. Here we identify an adenine base editor (ABE) and single-guide RNA system that can efficiently correct this human pathogenic mutation with minimal off-target and bystander editing. We show that delivery of base editing components rescues pathological manifestations of HCM in iPSC-cardiomyocytes derived from HCM patients and in a humanized mouse model of HCM. Our findings demonstrate the use of base editing to treat inherited cardiac diseases and prompt the further development of ABE-based therapies to correct a variety of monogenic mutations causing cardiac disease.
2022-10-25 | GSE201755 | GEO
Project description:Optimization of CRISPR/Cas9-mediated genome engineering has resulted in base editors that hold promise for mutation repair and disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived organoids. First we show Efficacy of cytosine and adenine base editors in modelingCTNNB1hot-spot mutations in hepatocyte organoids. Next, we use C>T base editors to insert nonsense mutations inPTENin endometrial organoids and demonstrate tumorigenicity even in the heterozygous state. Moreover, drug screening assays on organoids harboring eitherPTENorPTENandPIK3CAmutations reveal the mechanism underlying the initial stages of endometrial tumorigenesis. To further increase the scope of base editing we combine SpCas9 and SaCas9 for simultaneous C>T and A>G editing at individual target sites. Finally, we show that base editor multiplexing allow modeling of colorectal tumorigenesis in a single step by simultaneously transfecting sgRNAs targeting five cancer genes.
2023-07-30 | GSE236490 | GEO