Mechanism of antisense technology. Antisense RNA 2022-12-28

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Antisense technology is a method of gene regulation that involves the use of small, single-stranded oligonucleotides to specifically bind to and inhibit the expression of a specific gene. This is achieved by targeting the mRNA produced by the gene, which is the intermediate molecule that carries the genetic information from DNA to the ribosomes, where it is translated into a protein. By inhibiting the mRNA, antisense technology effectively prevents the gene from being expressed and the corresponding protein from being produced.

The mechanism of antisense technology relies on the specific base-pairing properties of nucleic acids. DNA and RNA are composed of a series of nucleotide bases (adenine, cytosine, guanine, and thymine in DNA; adenine, cytosine, guanine, and uracil in RNA) that are arranged in a specific sequence. The complementary base pairs are adenine and thymine, and cytosine and guanine. This means that if a single-stranded oligonucleotide containing a specific sequence of bases is designed to target a specific mRNA molecule, it will bind to it through base-pairing interactions.

Antisense oligonucleotides can be synthesized chemically or produced using in vitro transcription methods. Once they are synthesized, they are administered to cells or organisms in a variety of ways, including intravenous injection, oral delivery, and local delivery to specific tissues. The oligonucleotides are then taken up by cells and can bind to their target mRNA molecules.

There are several mechanisms by which antisense oligonucleotides can inhibit gene expression. One mechanism is by simply blocking the translation of the mRNA into protein. The oligonucleotide may bind to the mRNA molecule in such a way that it physically blocks the ribosome from accessing it and translating it into protein. Another mechanism is by causing the degradation of the mRNA molecule. The oligonucleotide may bind to the mRNA and recruit enzymes called ribonucleases, which can break down the mRNA and prevent it from being translated.

Antisense technology has many potential applications in the fields of medicine and biotechnology. It has been used to study gene function, to develop therapies for genetic diseases, and to produce genetically modified organisms with desired traits. However, there are also challenges to the use of antisense technology, including the potential for off-target effects and the difficulty of delivering the oligonucleotides to the appropriate cells in the body.

Overall, antisense technology is a promising approach to regulating gene expression and has the potential to revolutionize the treatment of genetic diseases and the production of genetically modified organisms. However, it is important to continue to explore the mechanisms of action and potential limitations of this technology to ensure its safe and effective use.

Antisense Oligonucleotides: Basic Concepts and Mechanisms

mechanism of antisense technology

We conclude with the prospective on the technology. This inhibition may be attributable to the disruption of the ribosomes or by physically blocking the initiation et al. The region responsible for this repression function was found to be a 300 base-pair locus upstream of the ompC promoter. The catalytic antisense strands are called ribozymes, which cuts the RNA molecules at specific position while the non catalytic antisense strand blocks the processing of RNA. Although the concept that ASO reagents only reduce expression of the targeted gene in a post-transcriptional manner has long been established, the effect and mechanism of ASO reagents on RNA polymerase II Pol II transcription are largely unknown.

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Antisense technology: A review

mechanism of antisense technology

A novel, and potentially remarkable, development in oligonucleotide technology is the relatively recent finding that 21—23-mer double-stranded RNA molecules, known as siRNA, can effectively silence gene expression m , and extremely specific, both with regard to mismatches and backbone. The majority of the antisense drugs investigated in the clinic function via an RNase H-dependent mechanism. The resulting RNA:RNA interaction is high affinity and results in inhibition of translation of that mRNA molecule. The 10th oligonucleotide therapy approved: golodirsen for duchenne muscular dystrophy. LNA-modified oligonucleotides mediate specific inhibition of microRNA function. The number of in vitro experiments has increased continuously, and this has led to numerous therapeutic trials, a few of which now appear preliminarily to be positive. These ASOs can usually only stop a disease from getting worse, but cannot often undo damage that has already been done.

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Antisense RNA

mechanism of antisense technology

Nusinersen versus Sham control in infantile-onset spinal muscular atrophy. Zamecnik and his colleagues at Massachusetts General Hospital found that, as the virus replicated, its RNA looped around on itself. Thus translation is halted. Stabilin-1 and stabilin-2 are specific receptors for the cellular internalization of phosphorothioate-modified antisense oligonucleotides ASOs in the liver. National Library of Medicine. Enhancement of SMN2 exon 7 inclusion by antisense oligonucleotides targeting the exon.

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Antisense technology: an overview and prospectus

mechanism of antisense technology

And Zamecnik the founder of Isis , now nearly 90 years old, is still researching antisense treatments for drug-resistant forms of tuberculosis and malaria. Moreover, the ASOs in development include additional mechanisms of action and routes of administration such as aerosol and oral formulations. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Once the ribosome binds the mRNA, it will translate to form functional protein. Targeted delivery of antisense oligonucleotides to pancreatic beta-cells.

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Antisense Drugs

mechanism of antisense technology

Cell 150, 883—894 2012. . Though, as the DNA is double helix, it can be used in the antisense technology; resulting in the formation of triplex. In fact, it is only the Sp phosphorothioate diastereomer that is nuclease resistant. Comparison of a phosphodiester and a phosphorothioate. The precise mechanism by which RNase H recognizes duplexes, however, is not well understood.

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Antisense Technology

mechanism of antisense technology

How do antisense oligonucleotides regulate gene expression? Definition, Designing Technology, and Mechanism Antisense drugs are drugs that seek to block DNA transcription or RNA translation in order to moderate many disease processes. Phosphorothioate modified oligonucleotide-protein interactions. However, there is a need in developing drugs that can activate or upregulate gene expression such as tumor suppressor genes, neuroprotective growth factors and genes that are found silenced in certain Mendelian disorders. Furthermore, in the past decade, the development of antisense oligonucleotide technologies as therapeutics agents has led to Food and Drug Administration approval for the commercialization of the first antisense oligonucleotide, Vitravene for cytomegalovirus retinitis; Refs. In contrast, the polysome profile with scrambled control oligonucleotide demonstrated that most of the full transcript could be found in the monosome or polysome fractions. Precise targeting of miRNA sites restores CFTR activity in CF bronchial epithelial cells.

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Antisense therapy

mechanism of antisense technology

Retrieved 22 September 2020— via GlobeNewswire. Retrieved 12 August 2020. It is one of the most approved approaches among several others, for inactivating a single chosen gene. We also consider strategic issues such as target selection and provide perspectives on the future of the field. How do ASO therapies work? What is antisense oligonucleotide technology? Therapeutic antisense oligonucleotides are coming of age. After post transcriptional modification, mRNA is transported out from nucleus to cytoplasm. Currently, the approach to restore deficient gene expression or protein function include enzyme replacement therapies, Despite the promises of asRNAs as drug targets or drug candidates, there are some challenges remained to be addressed.

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What are antisense oligonucleotides and how do they work?

mechanism of antisense technology

Once administered, the ASO is taken up into the cell via an as yet poorly defined endocytic mechanism and then enters the nucleus where it binds to its target pre-mRNA. This paper reviews the proteins to which PS ASOs bind and the effects of those interactions on the behaviours of both PS ASOs and the proteins. Article Summary: Antisense technology offers almost unlimited scope for the development of new methods of drug design. When antisense strand binds with the sense strand, there is a formation of duplex. Some characteristics of this type of asRNAs are described in the cis- and trans- acting asRNAs. .

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Antisense technology and gene silencing

mechanism of antisense technology

Many antisense sequences are usually tested to find the best candidate, since intra- and intermolecular interactions can affect oligonucleotide activity and delivery. This paper reports a clinical trial showing that nusinersen, an ASO that modulates the splicing of SMN2 , can safely improve motor neuron function in patients with SMA. Knockdown ASOs work by connecting to the mRNA and silencing the message by activating an enzyme that degrades the RNA. Some of these drugs have been designed to target viral disease and cancer cells in the body. Release 237, 1—13 2016.

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Antisense oligonucleotide technology can be used to investigate a circular but not linear RNA

mechanism of antisense technology

This review provides a comprehensive description of advances and outstanding questions with the application of siRNAs as therapeutics. Furthermore, in contrast to the steric-blocker oligonucleotides, RNase H-dependent oligonucleotides can inhibit protein expression when targeted to virtually any region of the mRNA. Cellular and Molecular Life Sciences. Methods in Molecular Biology Clifton, N. Thank you for visiting nature.

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