Oligonucleotide synthesis is the chemical synthesis of relatively short fragments of nucleic acids with defined chemical structure (sequence). … Typically, synthetic oligonucleotides are single-stranded DNA or RNA molecules around 15–25 bases in length.

Similarly, How do ASO drugs work?

The ASO drug nusinersen is an SSO that functions by blocking an intronic splicing silencer element in the SMN2 intron 7 preventing the spliceosome from excluding exon 7 (figure 1). The result of nusinersen action is expression of the functional, full-length SMN protein from the SMN2 gene.

Additionally, What is meant by oligonucleotide? An oligonucleotide is a compound comprised of about three to twenty nucleotides. Each monomeric unit component is comprised of a nucleobase, a pentose moiety, and phosphate group. Oligonucleotides are short DNA or RNA molecules. They readily bind to complementary oligonucleotides or to nucleic acids, forming a duplex.

What are Shortmers?

In each coupling cycle, a low percentage of the oligonucleotide chains do not extend, resulting in a mixture of full-length (n) and truncated (n-1, n-2, etc.) … sequences (‘shortmers’). In addition, small-molecule impurities are the byproduct of the cleavage and deprotection process.

What is Amidites?

amidite (plural amidites) (organic chemistry) Any ester of an oxyacid in which one or more -O- linkages are replaced by an -N< (amino) group.

What is the mechanism of action of Nusinersen?

The main pharmacological action mechanism of the 2Ęą-O-methoxyethyl phosphorothioate-modified drug nusinersen consists of an alteration of the SMN2 pre-RMA splicing process by inhibiting splicing factors. This facilitates the integration of exon 7 into the mRNA and thereby enhances full-length SMA protein levels.

What is an ASO drug?

ASO-based drugs employ highly modified, single-stranded chains of synthetic nucleic acids that achieve wide tissue distribution with very long half-lives.

How does antisense therapy work?

For antisense gene therapy, chemically engineered oligonucleotides complementary to specific mRNA are inserted into the cells which stop the translation of the specific protein. Similarly, the antisense drug contains the vital molecule—“the noncoding mRNA”—which blocks the translation of a specific protein.

What is oligonucleotide with example?

Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. … For example, an oligonucleotide of six nucleotides (nt) is a hexamer, while one of 25 nt would usually be called a “25-mer”.

What means oligo?

Oligo- (prefix): Means just a few or scanty. From the Greek “oligos’, few, scanty. Examples of terms starting with oligo- include oligodactyly (few fingers), oligohydramnios (too little amniotic fluid) and oligospermia (too few sperm).

What are polynucleotides in biology?

A polynucleotide is a compound comprised of several nucleotides (as opposed to oligosaccharides comprised of only a few, I.e. about three to twenty). Each monomeric component is comprised, in turn, of a nucleobase, a pentose moiety, and phosphate group.

What is desalting of DNA?

First, no inorganic salts, such as sodium or magnesium, are used when DNA is synthesized chemically. Our standard desalting step refers to the removal of small organic molecules left over from synthesis.

What is the function of a nucleotide?

A nucleotide is an organic molecule that is the building block of DNA and RNA. They also have functions related to cell signaling, metabolism, and enzyme reactions.

What is the meaning of DNA synthesis?

DNA synthesis is defined as the process by which copies of nucleic acids are strung together to form a longer DNA sequence within a laboratory setting. DNA synthesis processes. DNA oligomers are the foundation of the DNA synthesis process. The essential feature of DNA synthesis is that no naturally isolated DNA is used …

What is phosphoramidite method?

Phosphoramidite chemistry is the gold standard method for DNA synthesis that has been used in the industry for almost 35 years. Since its discovery, its simplicity and high efficiency have allowed large volumes of oligonucleotide sequences to be synthesized up to 200 base pairs in length.

What type of drug is Nusinersen?

Nusinersen injection is in a class of medications called antisense oligonucleotide inhibitors. It works by increasing the amount of a certain protein necessary for the muscles and nerves to work normally.

What is the mechanism of action for SPINRAZA?

Spinraza’s mechanism of action

Spinraza contains an antisense oligonucleotide (ASO), which controls the mutations caused in the chromosome 5q. This selectively binds and targets RNA and regulates gene expression. It has the potential to enhance the amount of functional SMN protein in infants and children with SMA.

What does Zolgensma do?

Zolgensma is an SMN-enhancing therapy that works by replacing the function of the missing or nonworking SMN1 gene with a new, working copy of an SMN gene. A virus, AAV9, carries the replacement gene into the body. This virus “infects” the cells with the new DNA.

What are aptamers used for?

In addition to facilitating biomarker identification, such aptamers can be directly used for cell isolation, cell visualization, and tracking cells in vivo. They can also be used to modulate activities of cell receptors and deliver different agents (e.g., siRNA and drugs) into the cells.

Who is aso?

Antistreptolysin O (ASO) is an antibody targeted against streptolysin O, a toxic enzyme produced by group A Streptococcus bacteria. ASO and anti-DNase B are the most common of several antibodies that are produced by the body’s immune system in response to a strep infection with group A Streptococcus.

Is siRNA a drug?

Small interfering RNA (siRNA) is a class of nucleic acid-based drugs (NABDs) able to block gene expression by interaction with mRNA before its translation. Small interfering RNAs (siRNAs) therefore present extraordinary potential due to their ability to silence the expression of disease-causing genes.

What is antisense therapy used for?

Antisense therapy is an approach to fighting diseases using short DNA-like molecules called antisense oligonucleotides. Recently, antisense therapy has emerged as an exciting and promising strategy for the treatment of various neurodegenerative and neuromuscular disorders.

How do antisense oligos work?

Antisense oligonucleotides intervene at a critical intermediate stage between DNA and proteins – where the DNA is converted into a molecule called messenger RNA (or mRNA for short). mRNA is very similar to DNA, but much less stable, and chemically very slightly different. It acts as the template for making proteins.

Is antisense therapy gene therapy?

Antisense gene therapy is a gene silencing technique similar to RNA interference, but uses a slightly different mechanism. The therapy is called a gene silencing technique because, instead of repairing the gene, it aims to “silence” the gene’s effect.