What is an ASO?
An antisense oligonucleotide is a single stranded DNA oligo, complementary to an mRNA target. When added to the cell, the ASO hybridizes to the target mRNA resulting in a short double-stranded section.
ASOs can be used to block the production of proteins and are currently being studied in the treatment of several disease types. As of 2020, more than 50 antisense oligonucleotides were in clinical trials.
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Enter your ASO sequence into our online tool for quick and easy ordering.
While there are no black and white rules for ASO design, there are some general guidelines:
- ASOs are designed to be approximately 20 bases long, designed in antisense orientation to the RNA of interest.
- ASO are often designed to target either the start codon (to block translation), or a splice site (to block splicing).
- It is strongly recommended to test multiple designs to find optimal sequences.
Additionally, the secondary and tertiary mRNA folding must be considered, as it could make the target sequence inaccessible to the ASO at certain locations. RNA folding software (e.g., Sfold or mfold) can help to assess the RNA structure to identify optimal targets1.
Finally, when comparing siRNA and ASOs it is important to note that while siRNA functions with RISC in the cytoplasm, ASOs can target mRNA in either the nucleus or cytoplasm.
ASOs are subject to nuclease degradation, so various modifications are often used to enhance the stability of the oligo.
Phosphorothioate linkages are one common ASO modifier. In addition to aiding stability, these modifications are thought to aid in the function in other ways, such as retaining the negative backbone charges which facilitates the oligo’s entry into the cell.
Other common modifications are the 2’-O-methyl modification, Locked Nucleic Acid modification, and MOE (methoxyethyl) modification. These modifications are often selected to increase resistance to nucleases, and also to potentially increase the melting temperature, or affinity of the oligo to the target mRNA.
Horizon offers custom ASO synthesis through our Dharmacon Custom Oligo Synthesis group.
Simply enter you sequence(s) into our ASO ordering tool, or contact scientific support with any questions.