Antisense therapy is a form of treatment for genetic disorders or infections. When the genetic sequence of a Particular gene is Known to be causative of a Particular disease, it is feasible to synthesize a strand of nucleic acid ( DNA, RNA or a similar chemical) 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 been translated. Alternatively, the strand might be targeted to a splicing site on pre-mRNA and modify the exon content of an mRNA. 
This synthesized nucleic acid is termed an “anti-sense” oligonucleotide (AON) because its base sequence is complementary to the gene messenger RNA (mRNA), which is called the “sense” sequence (so that a sense segment of mRNA “5 ‘ -AAGGUC-3 ‘”would be blocked by the anti-sense mRNA segment” 3′-UUCCAG-5’ “).
Antisense oligonucleotides have been researched as potential drugs    for diseases such as cancers (including lung cancer , colorectal carcinoma , pancreatic carcinoma , malignancy glioma and malignant melanoma ), diabetes , amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy , spinal muscular atrophy and diseases such as asthma , arthritis and pouchitis with an inflammatorycomponent. As of 2016, Several antisense drugs-have-been approved by the US 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.
Example antisense therapies
As of 2012, some 40 antisense oligonucleotides and siRNAs have been in clinical trials, including over 20 in advanced clinical trials (Phase II or III).  
Also in 2006, German physicians reported a dose-escalation study for the AP 12009 compound (a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of 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 US FDA in Aug 1998 as a treatment for cytomegalovirus retinitis .
In January 2013 mipomersen (Marketed as Kynamro) Was approved by the FDA for the treatment of homozygous familial hypercholesterolemia .  
Hemorrhagic fever viruses
In early 2006, scientists studying the Ebola hemorrhagic fever viruses at USAMRIID annoncé 75% recovery rate after-oven infecting rhesus monkeys And Then Treating Them with an antisense morpholino drug developed by Sarepta Therapeutics (formerly named AVI BioPharma ), a US biotechnology firm.  The general mortality rate for monkeys infected with Ebola virus is 100%. In late 2008, AVI BioPharma successfully filed Investigational New Drug(IND) applications with the FDA for its two lead products for Marburg and Ebola viruses. These drugs, AVI-6002 and AVI-6003 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-6002 and AVI-6003 demonstrated reproducible and high rates of survival in non-human primates challenged with a lethal infection of the Ebola and Marburg viruses, respectively. 
HIV / AIDS
Starting in 2004, researchers in the US have been conducting research on antisense technology to combat HIV. 
In the past, the virus has been harvested, modified with an antisense RNA virus viral envelope protein, and re-infused into the patient during a planned lapse in retroviral drug therapy. 
Spinal muscular atrophy
In 2004, development of an antisense therapy for spinal muscular atrophy was started. Over the Following years, an antisense oligonucleotide later named nusinersen Was developed by Ionis Pharmaceuticals under a licensing agreement with Biogen . In December 2016, nusinersen received regulatory approval of FDA for the treatment of spinal muscular atrophy.  
Duchenne muscular dystrophy
In September 2016, eteplirsen received FDA approval for the treatment of Duchenne muscular dystrophy .
Volanesorsen is in phase 3 clinical trials for hypertriglyceridemia as of December 2016.
Because nucleases that cleave the phosphodiester linkage in DNA are expressed in almost every cell, unmodified DNA molecules are degraded before they reach their targets. Therefore, antisense drug candidate molecules are modified Generally During the drug discovery stage of Their Development.   Additionally, most targets of antisense are located inside cells, and getting nucleic acids across cell membranes is also difficult. Therefore, most clinical candidates have modified DNA “backbones”, or the nucleobase or sugar moieties of the nucleotidesare altered. Additionally, other molecules May be conjugated to antisense molecules in order to Improve Their Ability to target some cells or to cross barriers like cell membranes or the blood brain barrier . 
- Oligonucleotide synthesis
- Antisense mRNA
- Peptide nucleic acid
- Locked nucleic acid
- RNA interference (which uses double-strand RNA)
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- Jump up^ Grant, Charley (2016-12-27). “Surprise Drug Approval Is Holiday Gift for Biogen” . Wall Street Journal . ISSN 0099-9660 . Retrieved 2016-12-27.
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