ASOsTherapySiRNASpinal musculaTherapeuticSiRNAsRNAsVitroMRNATherapiesDegradationComplementaryMixed-backbone2019ExonOligodeoxynucleotidesGenesMDM2MorpholinoMiceSynthesisAssaysPreclinicalToxicityPharmaceuticalsMoleculesProteinReductionProteinsCleavageAutoradiographyTreatmentsMutantTreatmentDevelopmentEffectsEffectiveDeliveryStudyDrugDrugsTarget
ASOs8
- Secarna Pharmaceuticals, an IZB-based biopharmaceutical company focusing on the discovery and development of next-generation antisense oligonucleotide (ASO) therapies to address challenging or previously undruggable targets via its LNAplus™ platform, announced the publication of striking new preclinical data demonstrating that bimodal ASOs can enable efficacious long-term antitumor immunity in tumor models compared to current immune checkpoint inhibitors. (izb-online.de)
- Antisense oligonucleotides (ASOs), defined as short synthetic oligonucleotides with single-stranded sequences complementary to certain mRNA sites, have been under drug development for approximately 30 years, with the first FDA-approved drug, Fomivirsen, being approved in 1998 ( Stein and Castanotto, 2017 ). (aspetjournals.org)
- Antisense oligonucleotides (ASOs) offer a new therapeutic strategy in Parkinson's disease (PD) because they can be readily targeted to genes causally linked to PD development or progression. (shakeitup.org.au)
- Antisense oligonucleotides (ASOs) are versatile agents for controlling the translation and splicing of mRNA. (elsevierpure.com)
- A novel approach to tritium-labeled antisense oligonucleotides (ASO) was established by conjugating N -succinimidyl propionate, as well as maleimide-derivatives, to the 3′-end of ASOs targeting metastasis-associated lung adenocarcinoma transcript 1 (Malat1) containing amino- or sulfhydryl-linkers. (springeropen.com)
- Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). (wikipedia.org)
- They include coding mRNAs and non-coding (nc) RNAs among them antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), micro-RNAs (miRNAs), small activating RNAs (saRNAs), RNA aptamers and RNA guides. (frontiersin.org)
- There are currently several products containing RNA on the market, and many are under development, among them mRNA, antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), small activating RNAs (saRNAs), micro-RNAs (mi-RNAs), RNA aptamers and RNA guides. (frontiersin.org)
Therapy10
- Antisense oligonucleotide (ASO) therapy has the potential to ameliorate many neurodegenerative diseases at the genetic level to suppress the production of harmful proteins or non-coding RNAs. (news-medical.net)
- Antisense Oligonucleotide Therapy for the Nervous System: From Bench to Bedside with Emphasis on Pediatric Neurology. (ntsad.org)
- Antisense oligonucleotide therapy plays a vital role in cancer and genetic disorders. (artofhealingcancer.com)
- This therapy involves the use of oligonucleotides that are complementary to specific target DNA or RNA in the nucleus. (artofhealingcancer.com)
- The use of oligonucleotides that are complementary to our target mRNA in order to reduce the expression of some specific gene in a cell is called antisense therapy. (artofhealingcancer.com)
- So, oligonucleotides used for antisense therapy should be modified in such a way that they have high stability and low side effects. (artofhealingcancer.com)
- The use of oligonucleotides for the treatment of cancer patients is found to be a very effective therapy. (artofhealingcancer.com)
- Antisense therapy is effective in the sense that it can distinguish between the normal and mutated oncogenes in cells and targets only mutated oncogenes without downregulating the expression of normal genes. (artofhealingcancer.com)
- In 2004, development of an antisense therapy for spinal muscular atrophy began. (wikipedia.org)
- Effective treatment of spinal muscular atrophy with antisense oligonucleotide therapy opens the door to treating other neurological disorders with this approach. (ox.ac.uk)
SiRNA1
- Examples of these RNA therapies include antisense oligonucleotide (ASO), small interfering RNA (siRNA), and microRNA (miRNA) therapies. (medlineplus.gov)
Spinal muscula1
- An antisense oligonucleotide drug has been approved by the Food and Drug Administration for treating spinal muscular atrophy, a hereditary disorder that causes arm and leg muscle weakness and deterioration in children. (sciencebeta.com)
Therapeutic3
- Therapeutic Oligonucleotides target the mRNA and change gene expression (proteins). (artofhealingcancer.com)
- Many antisense therapeutic drugs are available in the market and are being used for the treatment of multiple disorders like cancer, Alzheimer's disease, Parkinson's disease, and arthritis. (artofhealingcancer.com)
- Gendicine was the first antisense therapeutic drug that was approved for head and neck cancer in China. (artofhealingcancer.com)
SiRNAs2
- JHEP Live: Antisense oligonucleotides vs. siRNAs in the treatment of chronic hepatitis B: Who will be the winner, if at all? (easl.eu)
- In this JHEP Live the faculty will be discussing the use of antisense oligonucleotides and siRNAs in the treatment of chronic hepatitis B infections. (easl.eu)
RNAs2
- Unmodified RNA, RNA with modifications, chimeric oligonucleotides with mixed DNA and RNA bases, 2'-OMe-RNA, 2'-F-RNA, and other antisense RNAs are available at your specific request. (genscript.com)
- This can be done by chemically modifying the oligonucleotides like CpG, anti-gene, small non-coding RNAs, etc. (artofhealingcancer.com)
Vitro2
- Antisense mixed-backbone oligonucleotides (MBO) specifically inhibit MDM2 expression in a dose- and time-dependent manner, resulting in significant anti-tumor activity in vitro and in vivo. (nih.gov)
- Using viral RNA, Stephenson and Zamecnik ( 1978 ) demonstrated in 1978 that translation of proteins could be efficiently inhibited in vitro by competitive hybridization with antisense oligonucleotides (ASO). (springeropen.com)
MRNA6
- They comprise a few dozen base pairs arranged in an 'antisense' or reverse order and prevent production of pathogenic proteins through binding to the 'sense' strand of mRNA targets. (news-medical.net)
- These oligonucleotides bind in the 5 to 3 directions with mRNA and do not allow it to translate into proteins. (artofhealingcancer.com)
- modalities because oligonucleotides can easily be modified, they have a high affinity to bind targeted mRNA, they are highly specific, and have no side effects. (artofhealingcancer.com)
- The oligonucleotide sequence binds the mRNA in the cell and prevents the synthesis of specific proteins from it. (artofhealingcancer.com)
- This prevention may result when oligonucleotides cause inhibition of the translation process, they may prevent the spicing of exons, or they inhibit the transport of mRNA from the nucleus into the cytoplasm which is important for translation to occur. (artofhealingcancer.com)
- Antisense therapeutics are synthetic RNA mimetics that bind to mRNA via complementary base-pairing interactions to modulate transcription 1 . (nature.com)
Therapies1
- Rapid development of antisense therapies can enable on-demand responses to new viral pathogens and make personalized medicine for genetic diseases practical. (nature.com)
Degradation4
- The research team had recently developed DNA/RNA heteroduplex oligonucleotide (HDO) technology capable of highly efficient RNA degradation in vivo. (news-medical.net)
- Site-specific degradation of DNA was achieved by the use of DNA oligonucleotides covalently tethered to phenazine 5,10-di-N-oxide. (elsevierpure.com)
- Several parameters of DNA degradation were studied, including the effect on DNA degradation of chain length in the tether connecting the oligonucleotides and prosthetic group, the relative efficiencies of DNA cleavage when the prosthetic group was in the middle or at the end of the antisense oligonucleotide, and the effect of O 2 on DNA degradation. (elsevierpure.com)
- Also studied was the actual chemistry of DNA oligonucleotide degradation and the ability of individual diastereomers of the modified oligonucleotides to mediate degradation of the target DNA. (elsevierpure.com)
Complementary6
- Antisense 20-mer oligonucleotide complementary. (checkorphan.org)
- Oligonucleotides bind the complementary sequence and inhibit the synthesis of specific proteins by different mechanisms. (artofhealingcancer.com)
- The chemical modifications allow the oligonucleotides to enter the nucleus and bind their complementary RNA which is also an RNA of interest. (artofhealingcancer.com)
- The oligonucleotides are of specific sequences complementary to the target RNA or DNA sequence. (artofhealingcancer.com)
- So, there is no chance of multiple complementary sites for oligonucleotides in the genome and hence no harm to normal cells. (artofhealingcancer.com)
- When annealed to a complementary DNA target strand, the antisense oligonucleotide effected alkylation of guanosine residues in proximity to the phenazine di-N-oxide prosthetic group. (elsevierpure.com)
Mixed-backbone1
- The ocular disposition and toxicity of GEM132, a mixed backbone phosphorothioate oligonucleotide developed for the treatment of cytomegalovirus-induced retinitis, were studied in rabbits for 6 months following single intravitreal injection of 5, 20, or 100 μg/eye (toxicity) and 3.7, 15.7, or 78.5 μg/eye (disposition). (aspetjournals.org)
20192
- Liu, Z & Corey, DR 2019, CHAPTER 2: Mechanisms of Antisense Oligonucleotides . (elsevierpure.com)
- In 2019, a report was published detailing the development of milasen, an antisense oligonucleotide drug for Batten disease, under an expanded-access investigational clinical protocol authorized by the Food and Drug Administration (FDA). (wikipedia.org)
Exon3
- Using antisense oligonucleotides, we induce skipping of huntingtin exon 12 that encodes important cleavage sites. (bmj.com)
- Pilot studies in the YAC128 transgenic HD mouse model revealed skipping of human huntingtin exon 12 after a single intracerebroventricular injection of antisense oligonucleotides. (bmj.com)
- We have recently started a follow-up study to assess the longitudinal phenotypical effect of antisense oligonucleotide-mediated exon skipping in YAC128 HD mice. (bmj.com)
Oligodeoxynucleotides2
- Antisense oligodeoxynucleotides (AS-ODNs) have been widely used to determine gene function, validate drug targets and as novel therapeutics for human diseases. (uni-regensburg.de)
- Attenuation of matrix protein secretion by antisense oligodeoxynucleotides to the cyclin kinase inhibitor p21(Waf1/Cip1). (biomedcentral.com)
Genes2
- When oligonucleotide-based drugs are given to the cancer patient, the drugs target the specific mutated genes in cancerous cells. (artofhealingcancer.com)
- We will focus on the use of antisense oligonucleotides, cell cycle analysis, and luciferase reporter genes. (biomedcentral.com)
MDM23
- Considering the complexity of MDM2 functions, we have chosen to use gene silencing technologies including antisense oligonucleotides and RNA interference. (nih.gov)
- In this article, we summarize the investigation of the antisense technology for inhibiting MDM2 expression. (nih.gov)
- These results provide a basis for clinical evaluation of antisense anti-MDM2 oligonucleotides as chemosensitizers and radiosensitizers. (nih.gov)
Morpholino1
- Antisense phosphorodiamidate morpholino oligomers (PMOs) are promising candidates to fill such a role, but their challenging synthesis limits their widespread application. (nature.com)
Mice2
- They then tested oligonucleotides on two lines of mice genetically engineered to have problems associated with SCA2 by programming neurons in the cerebellum to make mutant ataxin 2. (sciencebeta.com)
- Compared to placebo, injections of the antisense oligonucleotides into the nervous system of the newborn mice extended their median lifespan by 35 percent and improved their ability to walk, while lowering ataxin 2 gene levels in the brain and spinal cord. (sciencebeta.com)
Synthesis1
- The intrathecally administered antisense oligonucleotide tofersen lowers synthesis of the superoxide dismutase 1 (SOD1) protein and is getting researched in patients with amyotrophic lateral sclerosis (ALS) involved with mutations in SOD1 ( SOD1 ALS). (innolabllc.com)
Assays1
- The method provides substantial improvements, including minimal matrix effects and high specificity when compared with previously used oligonucleotide ƒ u detection methods such as ligand binding assays or liquid scintillation. (aspetjournals.org)
Preclinical2
- Although these results are promising, rapid preclinical development of antisense drugs necessitates new technologies to enable high-throughput drug screening. (nature.com)
- Quality custom oligonucleotides for research and preclinical applications. (horizondiscovery.com)
Toxicity2
- While recent publications have shown promising results reducing mutant huntingtin toxicity by lowering huntingtin levels using antisense oligonucleotides, there is some concern regarding unwanted side effects caused by lowering huntingtin protein levels too much. (bmj.com)
- The safety and toxicity profile of SPL84, an inhaled antisense oligonucleotide for treatment of cystic fibrosis patients with the 3849 +10kb C->T mutation, supports a Phase 1/2 clinical study. (bvsalud.org)
Pharmaceuticals1
- Over the following years, an antisense oligonucleotide later named nusinersen was developed by Ionis Pharmaceuticals under a licensing agreement with Biogen. (wikipedia.org)
Molecules1
- For larger molecules such as oligonucleotides, however, the resulting molar specific activity after carbon-14 (62.4 mCi/mmol) labeling might be insufficient for a quantitative determination by liquid scintillation counting (LSC). (springeropen.com)
Protein1
- Antisense oligonucleotides (AO) have been shown to decrease apo(a) protein production in hepatocytes, which is the primary source of circulating Lp(a). (pace-cme.org)
Reduction2
- Apolipoprotein E4 Reduction with Antisense Oligonucleotides Decreases Neurodegeneration in a Tauopathy Model. (alzforum.org)
- Moreover, the target population for future trials on Lp(a) reduction with antisense oligonucleotides is currently hotly debated. (pace-cme.org)
Proteins1
- These are Oligonucleotides which cuts the expression of proteins with in a cell. (artofhealingcancer.com)
Cleavage1
- Nagai, K & Hecht, SM 1991, ' Site-specific DNA cleavage by antisense oligonucleotides covalently linked to phenazine Di-N-oxide ', Journal of Biological Chemistry , vol. 266, no. 35, pp. 23994-24002. (elsevierpure.com)
Autoradiography1
- In conclusion, this new method provides a powerful technique for fast and safe access to tritium-labeled oligonucleotides, e.g., for pharmacokinetic, mass balance, or autoradiography studies. (springeropen.com)
Treatments1
- Oligonucleotides are used in treatments for gene defects and Metabolic disorders. (artofhealingcancer.com)
Mutant1
- Antisense downregulation of mutant huntingtin in a cell model. (biomedcentral.com)
Treatment2
- The strength of such a strategy is highlighted by the emergence of SARS-CoV-2, wherein oligonucleotide-based drugs were among the first treatment types to enter human trials as early as 2 months after the virus's first reports 4 , 5 , 6 . (nature.com)
- SPL84 is an inhaled antisense oligonucleotide (ASO) in development for the treatment of cystic fibrosis (CF) patients carrying the 3849 + 10kb C->T (3849) mutation . (bvsalud.org)
Development1
- This platform could find broad application not only in designing new SARS-CoV-2 and DMD antisense therapeutics, but also for rapid development of PMO candidates to treat new and emerging diseases. (nature.com)
Effects1
- The oligonucleotides that are available naturally are usually unstable or with low stability and efficacy as they have a lot of side effects. (artofhealingcancer.com)
Effective3
- In both lines, the oligonucleotides appeared to be effective. (sciencebeta.com)
- Although PMOs are known to be effective antisense candidates, robust screening efforts for efficient transition to the clinic have remained elusive. (nature.com)
- A subline of the human B cell lymphoma DHL-4, grown in the artificial serum-free medium HB101, displayed a resistant phenotype to the activity of an antisense oligodeoxynucleotide (aODN) effective on the parental DHL-4 line. (mcmaster.ca)
Delivery1
- Gewirtz AM, Stein CA, Glazer PM. Facilitating oligonucleotide delivery: helping antisense deliver on its promise. (biomedcentral.com)
Study1
- The current study describes the implementation of a hybridization liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform for the direct quantitation of antisense oligonucleotide (ASO) ƒ u . (aspetjournals.org)
Drug2
- The type of drug they used is called an antisense oligonucleotide. (sciencebeta.com)
- To rapidly prototype potential PMO drug candidates, we report a fully automated flow-based oligonucleotide synthesizer. (nature.com)
Drugs1
- The common stem for antisense oligonucleotides drugs is -rsen. (wikipedia.org)
Target1
- the latter effected strand scission of the target DNA oligonucleotide. (elsevierpure.com)