What are antisense oligodeoxynucleotides?
Antisense oligodeoxynucleotides (ODNs) are short synthetic strands of DNA or analogs that consist of 15 to 20 nucleotides. They specifically target their complementary stretches of RNA by duplex formation and inhibit protein biosynthesis.
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.
What are antisense oligonucleotides used to treat?
et al. Pharmacology of a central nervous system delivered 2′-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates. J. Pharmacol.
How does ASO therapy 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.
What is an antisense drug?
Antisense drug: A medication containing part of the non-coding strand of messenger RNA (mRNA), a key molecule involved in the translation of DNA into protein. Antisense drugs hybridize with and inactivate mRNA. This stops a particular gene from producing the protein for which it holds the recipe.
Is antisense therapy safe?
Therefore, antisense oligonucleotides do appear to be a safe and effective means of gene delivery. They contain no viral sequences, do not generate a host immune response, and will not integrate into the host cell genome. They can be targeted to both replicating and nonreplicating cells.
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.
Are antisense oligonucleotides gene therapy?
Oligo means ‘small,’ because ASOs are made up of relatively few (usually fewer than 25) nucleotides. An ASO is a small string of DNA or RNA letters that can stick to the mRNA. While they act on genetic diseases, ASOs are not considered ‘gene therapy’ as they only make contact with RNA, not DNA.
How do Morpholinos work?
Morpholinos do not trigger the degradation of their target RNA molecules, unlike many antisense structural types (e.g., phosphorothioates, siRNA). Instead, Morpholinos act by “steric blocking”, binding to a target sequence within an RNA, inhibiting molecules that might otherwise interact with the RNA.
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.