This study addresses the challenges of aberrant pre-mRNA splicing in Pompe disease, caused by pathogenic variants in the acid α-glucosidase (GAA) gene. These variants often lead to the use of cryptic splice sites, resulting in disrupted protein production. The research proposes a pipeline to identify these splicing defects and correct them using antisense oligonucleotides (AONs).   The team developed a splicing assay to detect aberrant splicing patterns in patient-derived fibroblasts. …

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1. Background and Purpose: Antisense oligonucleotide (AO)-mediated exon skipping is a promising strategy for treating genetic disorders like Duchenne Muscular Dystrophy (DMD). This method alters dystrophin pre-mRNA splicing to create a shorter but functional protein, potentially converting severe DMD into a milder Becker Muscular Dystrophy (BMD) phenotype. The paper highlights the significance of skipping exons 45–55, a common mutation area that could help nearly half of DMD patients.   2. …

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We proudly present JIF Hub (Journal Impact Factors Hub), a user-friendly platform giving researchers instant access to Journal Impact Factors and key metrics. Whether you’re choosing where to publish or exploring journals in your field, JIF Hub has all the data you need.   What is JIF Hub? JIF Hub helps researchers efficiently find Journal Impact Factors by entering a journal's ISSN. It’s designed to simplify journal analysis and optimize …

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I took some notes from the article and am happy to share them with anyone interested! The Problem: Antisense oligonucleotides (ASOs), which are designed to target and regulate specific genes, face two critical barriers limiting their therapeutic effectiveness: "endosomal entrapment” and “inefficient nuclear localization”. Only a small percentage of ASOs escape from endosomes to the cytosol and nucleus, preventing them from effectively modulating gene expression. The Potential Solution: Improving the …

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Antisense oligonucleotides (ASOs) are promising for targeting diseases by modulating gene expression, even for genes previously considered "undruggable." ASOs enter cells through endocytosis but face challenges as they often get trapped in endosomes, limiting their therapeutic effect. Strategies to enhance endosomal escape, including using endosomal escape agents and non-viral delivery vehicles, are critical to increase their effectiveness. Despite some success, only 1-2% of ASOs reach the target mRNA in the …

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This paper investigates a potential treatment for facioscapulohumeral muscular dystrophy (FSHD), a genetic disorder caused by the improper expression of the DUX4 gene in muscles, leading to muscle weakness and deterioration. Currently, there is no molecular therapy to halt or slow the progression of FSHD. The researchers tested an antisense oligonucleotide (ASO) that targets and reduces the DUX4 transcript in a mouse model (ACTA1-MCM;FLExDUX4) that mimics FSHD. The ASO treatment, …

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Casimersen (AMONDYS 45™) is a therapeutic antisense oligonucleotide designed for patients with Duchenne Muscular Dystrophy (DMD) whose gene mutation is amenable to exon 45 skipping. DMD is a genetic disorder characterized by the absence of dystrophin, a crucial protein for muscle function. This results in progressive muscle degeneration and loss of mobility, eventually affecting the heart and lungs. Casimersen works by binding to the mutated pre-mRNA, skipping exon 45 to …

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This paper introduces a novel therapeutic approach for Duchenne Muscular Dystrophy (DMD) using NS-089/NCNP-02, an antisense oligonucleotide (ASO) designed to skip exon 44 of the dystrophin gene. DMD is a severe muscle disorder caused by mutations in the DMD gene, leading to a lack of dystrophin protein. Exon skipping helps to restore the reading frame of dystrophin, enabling the production of a shorter but functional dystrophin protein. The authors focused …

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The paper titled "Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges" explores an advanced therapeutic strategy for treating Duchenne Muscular Dystrophy (DMD), a severe genetic disorder caused by mutations in the dystrophin gene. This mutation leads to the absence of functional dystrophin protein, which is essential for maintaining muscle integrity. One emerging treatment method involves antisense oligonucleotide (AO)-mediated exon skipping, where specific exons are skipped …

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Duchenne Muscular Dystrophy (DMD) is a severe genetic disorder affecting males, characterized by muscle degeneration and early death. Antisense-mediated exon skipping therapy offers a new hope by producing a truncated but functional dystrophin protein. Casimersen (Amondys 45) specifically targets exon 45 of the dystrophin gene, which applies to about 8% of DMD patients. The drug was approved by the FDA in 2021, based on its promising preclinical and phase I/II …

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