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Antisense oligonucleotide therapy - Latest research and news | Nature
More functional genomics products RNA interference. Antisense oligos. Antisense oligonucleotides. Order now. Technical overview Antisense oligonucleotides ASOs are used to inhibit gene expression levels both in vitro and in vivo. Figure 1.
Antisense oligo—mediated cleavage of the target by RNase H. Phosphorothioates and chimeric oligos. Antisense therapy is a form of treatment for genetic disorders or infections. When the genetic sequence of a particular gene is known to cause a particular disease, it is possible to synthesize a strand of nucleic acid DNA , RNA or a chemical analogue that will bind to the messenger RNA mRNA produced by that gene and inactivate it, effectively turning that gene "off".
This is because mRNA has to be single stranded for it to be translated. Alternatively, the strand might be targeted to bind a splicing site on pre-mRNA and modify the exon content of an mRNA. Antisense oligonucleotides have been researched as potential drugs    for diseases such as cancers including lung cancer , colorectal carcinoma , pancreatic carcinoma , malignant glioma and malignant melanoma , diabetes , amyotrophic lateral sclerosis ALS , Parkinson's disease ,  Duchenne muscular dystrophy , spinal muscular atrophy , Ataxia-telangiectasia in vitro and diseases such as asthma , arthritis and pouchitis with an inflammatory component.
As of , several antisense drugs have been approved by the U. Food and Drug Administration FDA : fomivirsen as a treatment for cytomegalovirus retinitis , mipomersen for homozygous familial hypercholesterolemia , eteplirsen for Duchenne muscular dystrophy, and nusinersen for spinal muscular atrophy. Also in , German physicians reported on a dose-escalation study for the compound AP a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human transforming growth factor TGF-beta2 in patients with high grade gliomas. At the time of the report, the median overall survival had not been obtained and the authors hinted at a potential cure.
Fomivirsen marketed as Vitravene , was approved by the U.
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FDA in Aug as a treatment for cytomegalovirus retinitis. In January mipomersen marketed as Kynamro was approved by the FDA for the treatment of homozygous familial hypercholesterolemia. These drugs, AVI  and AVI are novel analogs based on AVI's PMO antisense chemistry in which anti-viral potency is enhanced by the addition of positively charged components to the morpholino oligomer chain. Preclinical results of AVI and AVI demonstrated reproducible and high rates of survival in non-human primates challenged with a lethal infection of the Ebola and Marburg viruses, respectively.
Starting in , researchers in the US have been conducting research on using antisense technology to combat HIV. Yoo, H. Pae, and C. Holt, C. Rovinson-Benion, and R. Kairemo, A. Jekunen, and M. Tenhunen , Dosimetry and Optimization of in vivo Targeting with Radiolabeled Antisense Oligodeoxynucleotides oligonucleotide radiotherapy.
Offensperger, W. Offensperger, C. Thoma, D. Moradpour, F. Raizada, H.
Antisense Technology, Part B: Applications, Volume 314
Wang, D. Lu, P. Reaves, and M. Antisense technology is the ability to manipulate gene expression within mammalian cells providing powerful experimental approaches for the study of gene function and gene regulation. For example, methods which inhibit gene expression permit studies probing the normal function of a specific product within a cell. Such methodology can be used in many disciplines such as pharmacology, oncology, genetics, cell biology, developmental biology, molecular biology, biochemistry, and neurosciences.
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