Antisense Oligonucleotides
Antisense Oligonucleotides (ASOs) usually refer to short, synthetic, single-stranded DNA or RNA (13-30 nucleotides). Following binding to the targeted mRNA or pre-mRNA, ASOs modulates RNA function by several different mechanisms.
1. ASOs can form an RNA–DNA hybrid that becomes a substrate for RNase H, resulting in target mRNA degradation.
2. ASOs can modulate gene expression via steric block of the ribosomal machinery, which can lead to reduced expression, modulation of splicing and/or restoration of a functional protein.
3. Binding of ASOs to pre-mRNA can alter splicing factor recruitment and regulate splicing events.
The first in vivo applications of ASOs showed limited clinical potential because of the high susceptibility of ASOs with an unmodified phosphoribose backbone to rapid degradation by endonucleases and exonucleases. The modifications in backbone, and sugar molecules give ASOs more affinity and stability. Phosphorodiamidate morpholino oligomers (PMO) are very resistant to nuclease and protease degradation and are mostly used in splicing modulation or translation inhibition. Chemical modifications at 2' position of ribose sugar ring such as 2’-O-methyl (2’-O-me), 2’-Fluoro (2’-F), 2’-O-methoxyethyl (2’-MOE) allow oligonucleotide to adopt RNA like C3’-endo sugar pucker, making it thermally stable.
Cy3 labled MDM4-targeting ASO sodium is a Cy3 labled MDM4-targeting ASO sodium.
MDM4-targeting ASO sodium is a 25mer antisense oligonucleotide targeting MDM4. MDM4-targeting ASO sodium induced exon 6 skipping, leading to nonsense-mediated decay of the mRNA transcript that excludes exon-6. In multiple human melanoma cell lines and in melanoma patient-derived xenograft (PDX) mouse models, MDM4-targeting ASO-mediated skipping of exon 6 decreased MDM4 abundance, inhibited melanoma growth, and enhanced sensitivity to MAPK-targeting therapeutics.
Atesidorsen sodium scrambled negative control is the sequence scrambled negative control of Atesidorsen sodium.
FAM labled Atesidorsen sodiumis a FAM labled Atesidorsen sodium.
Cy3 labled Atesidorsen sodium is a Cy3 labled Atesidorsen sodium.
Zorevunersen sodium scrambled negative control is the sequence scrambled negative control of Zorevunersen sodium.
- Formula: C204H263N63O114P20S20
- Molecular Weight: 7197.20
Zorevunersen is an antisense oligonucleotide targeting the Scn1a gene based on TANGO technology. Zorevunersen increases Scn1a mRNA transcripts and elevates the expression level of NaV1.1 protein. Zorevunersen restores the excitability of PV interneurons, thereby reducing seizures and prolonging survival in mice. Zorevunersen can be used for research on Dravet syndrome.
FAM labled Zorevunersen sodiumis a FAM labled Zorevunersen sodium.
Cy3 labled Zorevunersen sodium is a Cy3 labled Zorevunersen sodium.
Cobomarsen scrambled control is the negative control form of Cobomarsen (HY-132601), with the sequence: ACAUCAUAGUGACU. The modification method is the same as that of Cobomarsen. Cobomarsen sodium is an oligonucleotide inhibitor of miR-155 and can be used in the research of B-cell lymphoma.
- Formula: C230H290D27N72O123P19S15
- Molecular Weight: 7155.18
Tofersen-d27 (BIIB067-d27) is the deuterium labeled Tofersen (HY-132580). Tofersen (BIIB067) is an antisense oligonucleotide and SOD1 mRNA inhibitor with an IC50 of 320 pM. Tofersen mediates RNase H-dependent degradation of SOD1 mRNA to reduce SOD1 protein levels in cerebrospinal fluid and serum. Tofersen downregulates cerebrospinal fluid neurofilament light chain, neurofilament heavy chain, amyloid-beta 1-40, amyloid-beta 1-42, neuropeptide Y, ubiquitin C-terminal hydrolase L1, neuropentraxins 1, 2, R, corticotropin-releasing hormone, IL-15, and serum neurofilament light chain, neurofilament heavy chain. Tofersen can be used for the research of superoxide dismutase 1-associated amyotrophic lateral sclerosis.
SSO111 sodium, a 20mer fully modified antisense oligonucleotide, targets the oncogene?HER2. SSO111 sodium induces exon 15 skipping during splicing, leading to the generation of a novel mRNA transcript that excludes exon 15. SSO111 sodium downregulated HER2 mRNA, which resulted in the inhibition of proliferation and induction of apoptosis in HER2-overexpressing tumor cells.
- Molecular Weight: 6920.84
- Molecular Weight: 5290.25
EZN-2968 is an antisense oligonucleotide that specifically binds and inhibits the expression of HIF-1α mRNA. EZN-2968, inhibits tumor cell growth.
- Molecular Weight: 6913.93 (free acid)
Cepadacursen sodium is a liver-targeting antisense oligonucleotide (ASO), inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) protein synthesis. Cepadacursen sodium can be used for hypercholesterolemia research and the prevention of atherosclerotic cardiovascular disease (ASCVD).
