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.
- Formula: C₁₇₂H₂₁₇N₇₄O₈₂P₁₇S₁₇
- Molecular Weight: 5704.66
Mulnitorsen is an antisense non-coding mitochondrial RNA (ASncmtRNA) synthesis reducer. Mulnitorsen is an antitumor agent.
- Formula: C296H434N86O146P20S19
- Molecular Weight: 8761.80
Evazarsen is an angiotensinogen synthesis inhibitor and possesses antihypertensive properties.
- Formula: C238H335N67O113P16S15
- Molecular Weight: 6919.13
Bezeparsen is a PCSK9 synthesis inhibitor.
- Formula: C280H440N119O105P23
- Molecular Weight: 7865.60
Brogidirsen (NS 089; NCNP 02) is a a dual-targeting antisense oligonucleotide. Brogidirsen can induce dystrophin protein experession. Brogidirsen can be used for the research of Duchenne muscular dystrophy.
- Molecular Weight: 6732.81
Suvodirsen (WVE-210201) is a oligonucleotide. Suvodirsen has the potential for study Duchenne muscular dystrophy (DMD).
- Molecular Weight: 5462.34
IONIS-DNM2-2.5Rx (DYM101) is an antisense agent targeting dynamin 2. IONIS-DNM2-2.5Rx has the potential for the research of centronuclear myopathy (CNM).
GABA-T Scramble control ASO is a scrambled control antisense oligonucleotide with no complementarity to known genes. GABA-T Scramble control ASO can be used as a negative control for in vivo GABA-T (ABAT) knockdown to demonstrate the specificity of target reduction. GABA-T Scramble control ASO can be used in research related to metabolic diseases such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease.
BP1002 is an antisense oligonucleotide targeting BCL-2. BP1002 silences BCL-2 expression by targeting the translation initiation site of Bcl-2 mRNA. Its backbone carries ethoxy modifications, which confer nuclease resistance, reduce off-target effects, and lower toxicity. BP1002 prolongs survival in non-Hodgkin's lymphoma xenograft models. BP1002 can be used in studies of acute myeloid leukemia, aggressive non-Hodgkin's lymphoma, and Venetoclax (HY-15531)-resistant hematological malignancies.
ASO-5005 is a 20-mer Gapmer antisense oligonucleotide modified with locked nucleic acids (LNA), featuring a full phosphorothioate backbone, which targets BCL2 mRNA and BCL2L1 mRNA. ASO-5005 downregulates Bcl-2 expression via an RNase H-dependent mechanism, with its sequence fully complementary to BCL2 mRNA; it simultaneously downregulates Bcl-xL expression via an RNase H-dependent mechanism, with three mismatches between its sequence and BCL2L1 mRNA, while LNA modification enhances its activity against this mismatched target. ASO-5005 induces Apoptosis by activating Caspase-3 and cleaving ICAD. ASO-5005 does not significantly regulate the expression of Bcl-W, Survivin, Akt, or p53 in tumor cells. ASO-5005 can be used for research on breast cancer and non-small cell lung cancer.
G4232 is an immune-silent BCL2 antisense oligonucleotide that binds to BCL2 mRNA to induce target degradation and inhibit Bcl-2 protein translation. G4232 carries 5'-methylcytosine in its two CpG motifs, which eliminates CpG-mediated immunostimulatory activity and does not cause significant splenomegaly or elevated plasma IL-12 levels in SCID mice. G4232 induces Apoptosis. G4232 inhibits tumor growth in a melanoma xenograft model. G4232 can be used in studies of melanoma and prostate cancer.
ASO-4625 is a 20-nucleotide gapmer antisense oligonucleotide with a full phosphorothioate backbone and 2'-O-(2-methoxy) ethyl ribose modifications, which targets BCL2 mRNA and BCL2L1 mRNA. ASO-4625 downregulates Bcl-2 expression via an RNase H-dependent antisense mechanism with 100% complementarity, and downregulates Bcl-xL expression via the same mechanism with three mismatches. ASO-4625 induces Apoptosis and acts as a chemosensitizer. ASO-4625 does not significantly modulate the expression of Bcl-W, survivin, Akt, or p53 mRNA. ASO-4625 can be used in studies of breast cancer and non-small cell lung cancer.
Unconjugated/naked Zoratolimod (without SMCC linker) is unconjugated/naked Zoratolimod (HY-177973) (without SMCC linker). Zoratolimod can be used to synthesize antibody oligonucleotide conjugates (AOCs). Mozistobart zoratolimod (HY-177568) is used for cancer immunology research.
- Formula: C206H250F17N78O109P19S14
- Molecular Weight: 6923.02
Bampidirsen (WVE-N531) is an antisense oligonucleotide (ASO) with a phosphorodiamidate backbone. Bampidirsen specifically induces DMD exon 53 skipping, and it can be used for the research of Duchenne muscular dystrophy.
- Formula: C230H318N69O127P19S13
- Molecular Weight: 7086.71
Vadenersen is an inhibitor of MECP2 protein expression. Vadenersen has potential for research into Rett syndrome.
Unconjugated/naked Zotadirsen (without SMCC linker) represents the nucleic acid component of Zotadirsen (HY-177972), lacking both the amino group and the SMCC linker. Unconjugated/naked Zotadirsen (without SMCC linker) can be used for the synthesis of AOC reagents.
Mouse Tnf ASO is an antisense oligonucleotide (ASO) that targets the expression of mouse TNF-α. Mouse Tnf ASO reduces the tissue levels of various pro-inflammatory cytokines, Th1 cytokines and Th17 cytokines. Mouse Tnf ASO improves the clinical and histopathological severity of experimental colitis, including alleviating weight loss, diarrhea and intestinal protein loss. Mouse Tnf ASO can be delivered to activated colonic macrophages in mice via galactosylated low-molecular-weight chitosan nanocomplexes, with higher delivery efficiency compared to naked ASO. Mouse Tnf ASO can be used in the research of Crohn's disease.
- Formula: C243H374N132O76P20
- Molecular Weight: 6979.87
Pinzodirsen (Compound ENTR-Oligo-0034) is a dystrophia myotonica protein kinase (DMPK) steric blocker. Pinzodirsen reduces the nuclear sequestration of toxic DMPK mRNA with splicing factors such as MBNL1 via steric blocking/relocation, or interferes with the secondary structure of CUG repeat RNA, instead of being cleaved by RNase H, thereby ameliorating systemic aberrant splicing in DM1. Pinzodirsen is applicable to the research of myotonic dystrophy.
- Formula: C398H498N160O310P40(C2H4O)2n (n≈450)
Ldalaptican pegol (AON-D21; NOX-D21) is a PEGylated mixed RNA/DNA L-aptamer that specifically binds to complement C5a. Ldalaptican pegol binds to C5a and the C5a moiety on uncleaved C5, thereby blocking C5a signaling. This inhibition suppresses downstream inflammatory responses, immune cell infiltration and chemotaxis, the release of pro-fibrotic factors, and abnormalities in lipid metabolism signaling pathways. Ldalaptican pegol can also alleviate allograft rejection. Ldalaptican pegol can be used in research on inflammatory muscle diseases, Duchenne muscular dystrophy (DMD), diabetes, renal fibrosis, and allograft organ transplant rejection.
- Formula: C224H291N88O112P19S19
- Molecular Weight: 7205.96
Cleruvirsen is a hepatitis B virus surface antigen (HBsAg) inhibitor with anti-hepatitis B virus (HBV) activity. Cleruvirsen can be used for hepatitis B-related research[1].
