Antisense therapy is a form of treatment that uses antisense
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 ...
s (ASOs) to target
messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
(mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including
ribonuclease H
Ribonuclease H (abbreviated RNase H or RNH) is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly al ...
mediated decay of the pre-mRNA, direct steric blockage, and
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 ...
content modulation through
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 examples of first generation modifications include the addition of a phosphorothioate group (PS), methyl group, or nitrogen. The most common is the phosphorothioate group (PS) in which the oxygen atoms of a phosphodiester group are replaced with sulfur atoms, greatly improving efficacy and reducing degradation. Generation two is sugar-modified, focused on the ribose sugar of the nucleotide. This generation saw improved binding affinity while reducing degradation. Some examples of generation two modifications are the substitution of R group with morpholine group (MO) and the usage of phosphorodiamidate morpholino oligomer (PMO) and thiomorpholine oligomer (TMO) as linkages between the ribose sugar and phosphodiester group in the backbone. Generation three is nucleobase-modified, the least common type of modification. These modifications enhanced binding affinity and cell penetration while reducing degradation and off-target effects. Examples include the introduction of G-clamps, pseudoisocytosine, and the substitution of bases with amine, thione, halogen, alkyl, alkenyl, or alkynyl groups.
Pharmacokinetics and pharmacodynamics
Half-life and stability
ASO-based drugs employ highly modified, single-stranded chains of synthetic
nucleic acid
Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ...
s that achieve wide tissue distribution with very long half-lives.
For instance, many ASO-based drugs contain phosphorothioate substitutions and 2' sugar modifications to inhibit
nuclease
In biochemistry, a nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds that link nucleotides together to form nucleic acids. Nucleases variously affect single and ...
degradation enabling vehicle-free delivery to cells.
''In vivo'' delivery
Phosphorothioate ASOs can be delivered to cells without the need of a delivery vehicle. ASOs do not penetrate the
blood brain barrier
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells.
Blood is compo ...
when delivered systemically but they can distribute across the
neuraxis
The neuraxis, also known as the neuroaxis is the axis of the central nervous system. It extends from the brain to the spinal cord and denotes the direction in which the central nervous system lies in both development and in mature organisms. Ear ...
if injected in the
cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
typically by
intrathecal administration
Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space (sin. ''intrathecal space'') so that it reaches the cerebrospinal fluid (CSF). It is useful in several app ...
. Newer formulations using conjugated ligands greatly enhances delivery efficiency and cell-type specific targeting.
Approved therapies
Amyotrophic lateral sclerosis
Tofersen
Tofersen, sold under the brand name Qalsody, is a medication used for the treatment of amyotrophic lateral sclerosis (ALS). Tofersen is an antisense oligonucleotide that targets the production of superoxide dismutase 1, an enzyme whose mutant ...
(marketed as Qalsody) was approved by the FDA for the treatment of
SOD1- associated amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
(ALS) in 2023.
It was developed by Biogen under a licensing agreement with Ionis Pharmaceuticals. In trials the drug was found to lower levels of an ALS biomarker, neurofilament light change, and in long-term trial extensions to slow disease.
Under the terms of the FDA's accelerated approval program, a confirmatory study will be conducted in presymptomatic gene carriers to provide additional evidence.
Batten disease
Milasen is a novel individualized therapeutic agent that was designed and approved by the FDA for the treatment of
Batten disease. This therapy serves as an example of personalized medicine.
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
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA).
Milasen "itself remains an investigational drug, and it is not suited for the treatment of other patients with Batten's disease" because it was customized for a single patient's specific mutation.
However it is an example of
individualized genomic medicine therapeutical intervention.
Cytomegalovirus retinitis
Fomivirsen
Fomivirsen (brand name Vitravene) is an antisense antiviral drug that was used in the treatment of cytomegalovirus retinitis (CMV) in immunocompromised patients, including those with AIDS. It was administered via intraocular injection.
It was di ...
(marketed as Vitravene), was approved by the U.S. FDA in August 1998, as a treatment for
cytomegalovirus retinitis
Cytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the retina of the eye that can lead to blindness. Caused by human cytomegalovirus, it occurs predominantly in people whose immune system has been compromised, including 1 ...
.
Duchenne muscular dystrophy
Several
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 ...
oligos have been approved to treat specific groups of mutations causing
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 pe ...
. In September 2016,
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. ...
(ExonDys51) received FDA approval for the treatment of cases that can benefit from skipping exon 51 of the dystrophin transcript. In December 2019,
golodirsen
Golodirsen, sold under the brand name Vyondys 53, is a medication used for the treatment of Duchenne muscular dystrophy. It is an antisense oligonucleotide medication of phosphorodiamidate morpholino oligomer (PMO) chemistry.
The most common ...
(Vyondys 53) received FDA approval
for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript. In August 2020,
viltolarsen
Viltolarsen, sold under the brand name Viltepso, is a medication used for the treatment of Duchenne muscular dystrophy (DMD). Viltolarsen is a Morpholino antisense oligonucleotide.
The most common side effects include upper respiratory tract in ...
(Viltepso) received FDA approval for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript.
Familial chylomicronaemia syndrome
Volanesorsen
Volanesorsen, sold under the brand name Waylivra, is a triglyceride-reducing drug. It is a second-generation 2'-''O''-methoxyethyl (2'-MOE) chimeric antisense therapeutic oligonucleotide (ASO) that targets the messenger RNA for apolipoprotein ...
was approved by the
European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
(EMA) for the treatment of
familial chylomicronaemia syndrome
Familial may refer to:
* ''Familial'' (album), a 2010 studio album by Phil Selway
*Family, a group of people affiliated by consanguinity, affinity, or co-residence
*Family (biology), one of the eight major taxonomic ranks, classified between orde ...
in May 2019.
Familial hypercholesterolemia
In January 2013
mipomersen
Mipomersen (International Nonproprietary Name, INN; trade name Kynamro) is a drug used to treat homozygous familial hypercholesterolemia and is administered by subcutaneous injection. There is a serious risk of liver damage from this drug and it ...
(marketed as Kynamro) was approved by the FDA for the treatment of homozygous
familial hypercholesterolemia
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol (LDL cholesterol), in the blood and early cardiovascular diseases. The mos ...
.
Hereditary transthyretin-mediated amyloidosis
Inotersen
Inotersen, sold under the brand name Tegsedi, is a 2'-O-(2-methoxyethyl) (2'-MOE) antisense oligonucleotide medication used for the treatment of nerve damage in adults with hereditary transthyretin-mediated amyloidosis. The sequence is TCTTG ...
received FDA approval for the treatment of
hereditary transthyretin-mediated amyloidosis
Familial amyloid polyneuropathy, also called hereditary transthyretin amyloidosis (hATTR), or Corino de Andrade's disease, is an autosomal dominant neurodegenerative disease. It is a form of amyloidosis, and was first identified and described by ...
in October 2018.
The application for inotersen was granted
orphan drug
An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...
designation.
[ ] It was developed by Ionis Pharmaceuticals and licensed to
Akcea Therapeutics.
Patisiran
Patisiran, sold under the brand name Onpattro, is a medication used for the treatment of polyneuropathy in people with hereditary transthyretin-mediated amyloidosis, a fatal rare disease that is estimated to affect 50,000 people worldwide.
It i ...
(sold under Onpattro) was developed by
Alnylam Pharmaceuticals
Alnylam Pharmaceuticals, Inc. is an American biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics for genetically defined diseases. The company was founded in 2002 and is he ...
, and also approved for use in the US and EU in 2018 with orphan drug designation.
Its mechanism-of-action is the
active substance of
small interfering RNA (siRNA), which allows it to interfere with and block the production of
transthyretin
Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol' ...
. As such, it was the first FDA-approved siRNA therapeutic.
Spinal muscular atrophy
In 2004, development of an antisense therapy for
spinal muscular atrophy
Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common geneti ...
began. Over the following years, an
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 aci ...
later named
nusinersen
Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder.
Since the condition it treats ...
was developed by
Ionis Pharmaceuticals
Ionis Pharmaceuticals, Inc. is a biotechnology company based in Carlsbad, California, that specializes in discovering and developing RNA-targeted therapeutics. The company has three commercially approved medicines: Spinraza ( Nusinersen), Tegse ...
under a licensing agreement with
Biogen
Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, United States specializing in the discovery, development, and delivery of the treatment of neurological diseases to patients worldwide. Biogen ope ...
. In December 2016, nusinersen received regulatory approval from
FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
and soon after, from other regulatory agencies worldwide.
Investigational therapies
Current clinical trials
As of 2020 more than 50 antisense oligonucleotides were in clinical trials, including over 25 in
advanced clinical trials (phase II or III).
Phase III trials
= Hereditary transthyretin-mediated amyloidosis
=
A follow-on drug to Inotersen is being developed by Ionis Pharmaceuticals and under license to
Akcea Therapeutics for hereditary transthyretin-mediated amyloidosis. In this formulation the ASO is conjugated to
N-Acetylgalactosamine enabling hepatocyte-specific delivery, greatly reducing dose requirements and side effect profile while increasing the level of
transthyretin
Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol' ...
reduction in patients.
= Huntington's disease
=
Tominersen (also known as IONIS-HTT
Rx and RG6042) was tested in a phase 3 trial for
Huntington's disease
Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly Genetic disorder#Autosomal dominant, inherited. It typically presents as a triad of progressive psychiatric, cognitive, and ...
although this trial was discontinued on March 21, 2021, due to lack of efficacy. It is currently licensed to
Roche
F. Hoffmann-La Roche AG, commonly known as Roche (), is a Switzerland, Swiss multinational corporation, multinational holding healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, ...
by Ionis Pharmaceuticals.
Phase I and II trials
Clinical trials are ongoing for several diseases and conditions including:
Acromegaly
Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There ...
,
age related macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Some people experien ...
,
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
,
amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
,
autosomal dominant retinitis pigmentosa,
beta thalassemia
Beta-thalassemia (β-thalassemia) is an genetic disorder, inherited hemoglobinopathy, blood disorder, a form of thalassemia resulting in variable outcomes ranging from clinically asymptomatic to severe anemia individuals. It is caused by reduce ...
,
cardiovascular disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
, elevated level of
lipoprotein(a)
Lipoprotein(a) is a low-density lipoprotein variant containing a protein called apolipoprotein(a). Genetic and epidemiological studies have identified lipoprotein(a) as a risk factor for atherosclerosis and related diseases, such as coronary h ...
,
centronuclear myopathy
Centronuclear myopathies (CNM) are a group of congenital myopathies where cell nuclei are abnormally located in the center of muscle cells instead of their normal location at the periphery.
Symptoms of CNM include severe hypotonia, hypoxia-req ...
,
coagulopathies,
cystic fibrosis
Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
,
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 pe ...
,
diabetes
Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
,
epidermolysis bullosa dystrophica
Epidermolysis bullosa dystrophica or dystrophic EB (DEB) is an inherited disease affecting the skin and other organs.
"Butterfly child" is the colloquial name for children born with the disease, as their skin is seen to be as delicate and frag ...
,
familial chylomicronemia syndrome
Lipoprotein lipase deficiency is a genetic disorder in which a person has a defective gene for lipoprotein lipase, which leads to very high triglycerides, which in turn causes stomach pain and deposits of fat under the skin, and which can lead t ...
,
frontotemporal dementia
Frontotemporal dementia (FTD), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of the brain's frontal lobe, frontal and tempor ...
,
Fuchs' dystrophy
Fuchs dystrophy, also referred to as Fuchs endothelial corneal dystrophy (FECD) and Fuchs endothelial dystrophy (FED), is a slowly progressing corneal dystrophy that usually affects both eyes and is slightly more common in women than in men. Althou ...
,
hepatitis B
Hepatitis B is an infectious disease caused by the '' hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. ...
,
hereditary angioedema
Hereditary angioedema (HAE) is a disorder that results in recurrent attacks of severe swelling. The swelling most commonly affects the arms, legs, face, intestinal tract, and airway. If the intestinal tract is affected, abdominal pain and vo ...
,
hypertension
Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
,
IgA nephropathy
IgA nephropathy (IgAN), also known as Berger's disease () (and variations), or synpharyngitic glomerulonephritis, is a kidney disease, disease of the kidney (or nephropathy) and the immune system; specifically it is a form of glomerulonephritis o ...
,
Leber's hereditary optic neuropathy
Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; it predomin ...
,
multiple system atrophy
Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by tremors, slow movement, muscle rigidity, postural instability (collectively known as parkinsonism), autonomic dysfunction and ataxia. This is caused by progr ...
,
non-alcoholic fatty liver disease
An alcohol-free or non-alcoholic drink, also known as a temperance drink, is a version of an alcoholic drink made without alcohol, or with the alcohol removed or reduced to almost zero. These may take the form of a non-alcoholic mixed drink or n ...
,
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
,
prostate cancer
Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...
,
Stargardt disease
Stargardt disease is the most common inherited single-gene retinal disease. In terms of the first description of the disease, it follows an autosomal recessive inheritance pattern, which has been later linked to bi-allelic ABCA4 gene variants ...
,
STAT3-expressing cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
s,
Usher syndrome
Usher syndrome, also known as Hallgren syndrome, Usher–Hallgren syndrome, retinitis pigmentosa–dysacusis syndrome or dystrophia retinae dysacusis syndrome, is a rare genetic disorder caused by a mutation in any one of at least 11 genes result ...
.
Preclinical development
Several ASOs are currently being investigated in disease models for
Alexander disease
Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins durin ...
,
ATXN2 (gene) and
FUS (gene)
RNA-binding protein fused in sarcoma/translocated in liposarcoma (FUS/TLS), also known as heterogeneous nuclear ribonucleoprotein P2 is a protein that in humans is encoded by the ''FUS'' gene.
Discovery
FUS/TLS was initially identified as a fus ...
amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
,
Angelman syndrome
Angelman syndrome (AS) is a genetic disorder that affects approximately 1 in 15,000 individuals. AS impairs the function of the nervous system, producing symptoms, such as severe intellectual disability, developmental disability, limited to no ...
,
Lafora disease
Lafora disease is a rare, autosomal recessive genetic disorder which results in myoclonus epilepsy and usually results in death several years after the onset of symptoms. The disease is characterized by the accumulation of inclusion bodies, kno ...
,
lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
,
multiple myeloma
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...
,
myotonic dystrophy
Myotonic dystrophy (DM) is a type of muscular dystrophy, a group of genetic disorders that cause progressive muscle loss and weakness. In DM, muscles are often myotonia, unable to relax after contraction. Other manifestations may include catarac ...
,
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
,
Pelizaeus–Merzbacher disease
Pelizaeus–Merzbacher disease is an X-linked neurological disorder that damages oligodendrocytes in the central nervous system. It is caused by mutations in proteolipid protein 1 (''PLP1''), a major myelin protein. It is characterized by a decr ...
, and
prion disease
Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of progressive, incurable, and fatal conditions that are associated with the prion hypothesis and affect the brain and nervous system of many animals, in ...
,
Rett syndrome
Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6–18 months of age and almost exclusively in girls. Symptoms include impairments in language and coordination, and repetitive movements. Those affected often h ...
,
spinocerebellar Ataxia Type 3.
See also
*
Antisense
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, ...
*
Antisense mRNA
*
Locked nucleic acid
A locked nucleic acid (LNA), also known as bridged nucleic acid (BNA), and often referred to as inaccessible RNA, is a modified RNA nucleotide in which the ribose moiety is modified with an extra bridge connecting the 2' oxygen and 4' carbon. The ...
*
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 ...
*
Oligonucleotide synthesis
Oligonucleotide synthesis is the chemical synthesis of relatively short fragments of nucleic acids with defined chemical structure (sequence). The technique is extremely useful in current laboratory practice because it provides a rapid and inexpens ...
*
Peptide nucleic acid
Peptide nucleic acid (PNA) is an artificially synthesized polymer similar to DNA or RNA.
Synthetic peptide nucleic acid oligomers have been used in recent years in molecular biology procedures, diagnostic assays, and antisense therapies. Due to ...
*
RNA interference
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...
(which uses ''double-strand'' RNA)
References
External links
Antisense Pharma: Promising Phase IIb Results Of Targeted Therapy With AP 12009 In Recurrent Anaplastic Astrocytoma
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Applied genetics
Biotechnology
Therapeutic gene modulation