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Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-mRNA, direct steric blockage, and exon content modulation through splicing site binding on pre-mRNA. [1]
Antisense oligonucleotides can be used to target a specific, complementary (coding or non-coding) RNA. If binding takes place this hybrid can be degraded by the enzyme RNase H. [12] RNase H is an enzyme that hydrolyzes RNA, and when used in an antisense oligonucleotide application results in 80-95% down-regulation of mRNA expression. [6]
AsRNA is transcribed from the lagging strand of a gene and is complementary to a specific mRNA or sense transcript. Antisense RNA (asRNA), also referred to as antisense transcript, [1] natural antisense transcript (NAT) [2] [3] [4] or antisense oligonucleotide, [5] is a single stranded RNA that is complementary to a protein coding messenger RNA (mRNA) with which it hybridizes, and thereby ...
Control oligos with irrelevant sequences usually produce no change in embryonic phenotype, evidence of the Morpholino oligo's sequence-specificity and lack of non-antisense effects. The dose required for a knockdown can be reduced by coinjection of several Morpholino oligos targeting the same mRNA, which is an effective strategy for reducing or ...
Antisense oligonucleotides (ASOs) inhibit the production of apolipoprotein(a) and reduce Lpa by up to 80 percent or more in trials. RNAi are small, interfering RNA molecules that silence the gene ...
Gapmer antisense oligonucleotides (ASOs) have the potential to cause unintended, off-target effects. These off-target effects are produced when the gapmer binds to mRNA with a sufficient degree of complementarity to the target mRNA, blocking or down-regulating the translation of unintended proteins. [12]
Automated synthesizers have revolutionized this process, allowing for rapid, scalable production of oligonucleotides with high purity and precision. Advancements in oligonucleotide synthesis have enabled the development of various therapeutic modalities, including antisense oligonucleotides, small interfering RNA (siRNA), and aptamers.
Antisense oligonucleotides were discovered in 1978 by Paul Zamecnik and Mary Stephenson. [5] Oligonucleotides, which are short nucleic acid fragments, bind to complementary target mRNA molecules when added to the cell. [5] [6] These molecules can be composed of single-stranded DNA or RNA and are generally 13–25 nucleotides long.
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