Catalog

Antisense oligonucleotides/Splice-switching oligonucleotides / Antagomirs

Antisense oligonucleotides (ASO) are short oligonucleotides (15-25 bases) complementary to an RNA of interest that induce RNA degradation by recruiting RNase H. Several other subtypes of ASOs were developed to date. One is splice-switching antisense oligonucleotide, which is complementary to pre-mRNA and change its splicing by blocking RNA-RNA or protein-RNA interactions that occur between components of the splicing machinery and the pre-mRNA. Also, antagomirs are synthetic antisense oligonucleotide, which are complementary to miRNA and block miRNA binding to mRNA targets. For efficient and potent knockdown of the target RNA, ASOs should be chemically modified to increase nuclease stability, decrease immune response and improve pharmacological properties. Introduction of 2′-O-methoxyethyl (2′-MOE) or Affinity Plus Locked Nucleic Acid (LNA) nucleotides in chimeric gapmer ASO also increase affinity to the target RNA (melting temperature of a heteroduplex).

We provide services for design and synthesis of ASO/splice-switching oligonucleotides/antagomirs for in vitro and in vivo studies. If you require assistance, especially regarding the feasibility of manufacturing ASO with non-standard modifications, please contact us via [email protected].

Gapmer ASO for downregulation of gene expression in vitro or in vivo
Active both in the nucleus and in cytoplasm [https://doi.org/10.1093/nar/gkv1206]
SSO for targeting alternative splicing events
Antagomirs for blocking microRNA

- ASO-based modulation of gene expression can be performed both in cell nucleus and cytoplasm. ASO recognize and hybridize to target mRNAs, which leads to cleavage of the mRNA by RNase H. Splice-switching oligonucleotides are typically 15–30 nucleotides long and designed to block the binding of splicing factors to the pre-mRNA, that alters the recognition of splice sites by the spliceosome and leads to an alteration of normal splicing of the targeted transcript. Antagomirs are synthetic antagonists of miRNA, which inhibits miRNA function. All these approaches are widely used in research and development of therapeutics.
- Engineered oligonucleotides should contain modified nucleotides to improve stability and affinity to the target RNA. Antisense oligonucleotides usually contain 2’-O-methylnucleosides, 2′-O-methoxyethyl (2′-MOE) nucleotides, conformationally blocked nucleosides (LNA, ENA, etc) and phosphorothioates.
- Design of antisense oligonucleotides rely on prediction of specificity within a transcriptome, melting temperature, content of guanosines and-cytosines, the length of oligonucleotides, as well as secondary structures of ASO and target RNA.

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