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Eteplirsen
Eteplirsen (brand name Exondys 51) is a medication to treat, but not cure, some types of Duchenne muscular dystrophy (DMD), caused by a specific mutation. Eteplirsen only targets specific mutations and can be used to treat about 14% of DMD cases. Eteplirsen is a form of antisense therapy. Eteplirsen was developed by Steve Wilton, Sue Fletcher and colleagues at the University of Western Australia and commercialized by Sarepta Therapeutics. After a controversial debate surrounding the drug's efficacy, during which two FDA review panel members resigned in protest, eteplirsen received accelerated approval from the US Food and Drug administration in late 2016. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) refused to authorize the use of eteplirsen. Adverse effects The following adverse events were observed in at least 10% of people who received eteplirsen in trials: vomiting, contusion, excoriation, arthralgia, rash, catheter site pai ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy predominantly affecting boys. The onset of muscle weakness typically begins around age four, with rapid progression. Initially, muscle loss occurs in the thighs and pelvis, extending to the arms, which can lead to difficulties in standing up. By the age of 12, most individuals with Duchenne muscular dystrophy are unable to walk. Affected muscles may appear larger due to an increase in fat content, and scoliosis is common. Some individuals may experience intellectual disability, and females carrying a single copy of the mutated gene may show mild symptoms. Duchenne muscular dystrophy is caused by mutations or deletions in any of the 79 exons encoding the large dystrophin protein, which is essential for maintaining the muscle fibers' cell membrane integrity. The disorder follows an X-linked recessive inheritance pattern, with approximately two-thirds of cases inherited from the mother and one-third res ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sarepta Therapeutics
Sarepta Therapeutics, Inc. is a medical research and drug development company with corporate offices and research facilities in Cambridge, Massachusetts, United States. Incorporated in 1980 as AntiVirals, , archiveurl = http://www.gene-tools.com/sites/default/files/Summerton2005_IPT.pdf shortly before going public the company changed its name from AntiVirals to AVI BioPharma soon with stock symbol AVII and in July 2012 changed name from AVI BioPharma to Sarepta Therapeutics and SRPT respectively. As of 2023, the company has four approved drugs (see the Products section below). History Sarepta started in Corvallis, Oregon on January 1, 1980 and was originally named Antivirals Inc. After occupying several research laboratory spaces in Corvallis, the company opened a production laboratory in Corvallis in February 2002 and was renamed AVI BioPharma Inc. The company made headlines in 2003 when it announced work on treatments for severe acute respiratory syndrome (SARS) and the West N ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Exon-skipping
In molecular biology, exon skipping is a form of RNA splicing used to cause cells to “skip” over faulty or misaligned sections (exons) of genetic code, leading to a truncated but still functional protein despite the genetic mutation. Mechanism Exon skipping is used to restore the reading frame within a gene. Genes are the genetic instructions for creating a protein, and are composed of introns and exons. Exons are the sections of DNA that contain the instruction set for generating a protein; they are interspersed with non-coding regions called introns. The introns are later removed before the protein is made, leaving only the coding exon regions. Splicing naturally occurs in pre-mRNA when introns are being removed to form mature-mRNA that consists solely of exons. Starting in the late 1990s, scientists realized they could take advantage of this naturally occurring cellular splicing to downplay genetic mutations into less harmful ones. The mechanism behind exon skipping is a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antisense Therapy
Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-mRNA, direct steric blockage, and exon content modulation through Splicing (genetics), splicing site binding on pre-mRNA. Several ASOs have been approved in the United States, the European Union, and elsewhere. Nomenclature The common stem for antisense oligonucleotides drugs is -rsen. The substem -virsen designates antiviral antisense oligonucleotides. Antisense Oligonucleotide Development Developments in ASO modification are separated into three generations. Generation one is called backbone-modified and focuses on the phosphodiester group of the nucleotide. This impacts inter-nucleotide binding. These modifications led to better distribution, reduced urinary excretion, and prolonged residence time of the ASOs in the cell. Some exam ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sue Fletcher
Sue Fletcher is an Australian scientist who is a professor and lecturer at the University of Western Australia and a Senior Principal Research Fellow at Murdoch University. She studies the field of molecular and cell biology and holds the position of chief scientific officer at PYC therapeutics. Currently her research is focused on inherited retinal disease, the central nervous system and neurodegeneration. Alongside Professor Steve Winton she developed novel treatments for Duchenne muscular dystrophy, including eteplirsen, which was the first of its kind to be approved by the FDA in 2016. In 2021 she was appointed an Officer of the Order of Australia for "distinguished service to medical research, to neurological science, and to the treatment and support of those with Muscular Dystrophy". Career and research Fletcher completed an undergraduate degree at the University of Zimbabwe. She then moved to Perth, where she completed a PhD at the University of Western Australia, with he ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antisense Oligonucleotide
Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small fragments of nucleic acids can be manufactured as single-stranded molecules with any user-specified sequence, and so are vital for artificial gene synthesis, polymerase chain reaction (PCR), DNA sequencing, molecular cloning and as molecular probes. In nature, oligonucleotides are usually found as small RNA molecules that function in the regulation of gene expression (e.g. microRNA), or are degradation intermediates derived from the breakdown of larger nucleic acid molecules. Oligonucleotides are characterized by the sequence of nucleotide residues that make up the entire molecule. The length of the oligonucleotide is usually denoted by " -mer" (from Greek ''meros'', "part"). For example, an oligonucleotide of six nucleotides (nt) is a hexamer, while one of 25 nt ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Morpholino
A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. Its molecular structure contains DNA bases attached to a backbone of methylenemorpholine rings linked through phosphorodiamidate groups. Morpholinos block access of other molecules to small (~25 base) specific sequences of the base-pairing surfaces of RNA, ribonucleic acid (RNA). Morpholinos are used as research tools for reverse genetics by gene knockdown, knocking down gene function. This article discusses only the Morpholino antisense oligomers, which are Nucleic acid analogues, nucleic acid analogs. The word "Morpholino" can occur in other chemical names, referring to chemicals containing a six-membered morpholine ring. To help avoid confusion with other morpholine-containing molecules, when describing oligos "Morpholino" is often capitalized as a trade name, but th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oligonucleotide
Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, Recombinant DNA, research, and Forensic DNA, forensics. Commonly made in the laboratory by Oligonucleotide synthesis, solid-phase chemical synthesis, these small fragments of nucleic acids can be manufactured as single-stranded molecules with any user-specified sequence, and so are vital for artificial gene synthesis, polymerase chain reaction (PCR), DNA sequencing, molecular cloning and as Fluorescence in situ hybridization, molecular probes. In nature, oligonucleotides are usually found as small RNA molecules that function in the regulation of gene expression (e.g. microRNA), or are degradation intermediates derived from the breakdown of larger nucleic acid molecules. Oligonucleotides are characterized by the Nucleic acid sequence, sequence of nucleotide residues that make up the entire molecule. The length of the oligonucleotide is usually denoted by "Monomer, -m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Intravenous Therapy
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water per os, by mouth. It may also be used to administer pharmaceutical drug, medications or other medical therapy such as blood transfusion, blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use. The intravenous route is the fastest way to deliver medications and fluid replacement throughout the body as they are introduced directly into the circulatory system and thus quickly distributed. For this reason, the intravenous route ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature RNA. Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome. History The term ''exon'' is a shortening of the phrase ''expressed region'' and was coined by American biochemist Walter Gilbert in 1978: "The notion of the cistron... must be replaced by that of a transcription unit containing regions which will be lost from the mature messengerwhich I suggest we call introns (for intragenic regions)alternating with regions which will be expressedexons." This definition was originally made for protein-coding transcripts that are spliced before b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nonsense Mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a ''nonsense codon'', or a premature stop codon in the transcribed mRNA, and leads to a truncated, incomplete, and possibly nonfunctional protein product. Nonsense mutations are not always harmful; the functional effect of a nonsense mutation depends on many aspects, such as the location of the stop codon within the coding DNA. For example, the effect of a nonsense mutation depends on the proximity of the nonsense mutation to the original stop codon, and the degree to which functional subdomains of the protein are affected. As nonsense mutations leads to premature termination of polypeptide chains; they are also called chain termination mutations. Missense mutations differ from nonsense mutations since they are point mutations that exhibit a single nucleotide change to cause substitution of a different amino acid. A nonsense mutation also differs from a nonstop mutation, which is a point muta ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Stop Codon
In molecular biology, a stop codon (or termination codon) is a codon (nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide chain, which may ultimately become a protein; stop codons signal the termination of this process by binding release factors, which cause the ribosomal subunits to disassociate, releasing the amino acid chain. While start codons need nearby sequences or initiation factors to start translation, a stop codon alone is sufficient to initiate termination. Properties Standard codons In the standard genetic code, there are three different termination codons: Alternative stop codons There are variations on the standard genetic code, and alternative stop codons have been found in the mitochondrial genomes of vertebrates, '' Scenedesmus obliquus'', and '' Thraustochytrium''. Reassigned ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
