A closer look at the Dharmacon™ antisense oligonucleotide (ASO) ordering tool

Our new Dharmacon™ ASO ordering tool is an online platform created for immediate price quoting and ordering of antisense oligonucleotides. With this custom DNA synthesis tool, you are able to create ASOs with a variety of chemical modifications at a scale and purity to meet your customized needs.

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Antisense oligonucleotides are an emerging therapeutic platform used in the general sense for the treatment of genetic diseases. ASOs function to target messenger RNA (mRNA) as a means of altering mRNA expression via several mechanisms of action and therefore offer promise for the treatment of many types of genetic diseases.

Challenges in clinical efficacy, hepatic toxicology, nephrotoxicity, off-target side effects, and sufficient biological activity have been barriers to therapeutic approval for the past two decades. Further adjustments to peptide nucleic acids, locked nucleic acids (LNAs), ribose, and nucleobases result in improvements in the pharmacokinetic profile. Improvements in affinity and permeability coupled with increased resistance to endonuclease-mediated degradation have improved ASO delivery and stability, resulting in stronger efficacy in the clinical setting. The challenges associated with safety and efficacy have, to date, delayed wide-spread adoption and regulatory approval. However, with data to support improved safety and efficacy based on chemical and structural modifications, it illustrates a bright future perspective for this emerging modality.

RNA functions as an intermediary between genetic sequences and the process of protein synthesis. As a means of controlling the expression of genes within cells, ASOs, also referred to as antisense oligos, can be used to treat a wide range of genetic diseases including those originating from single point mutations or those with multifactorial causes. Simply put, ASOs can be used to reduce the protein levels of a gene of interest by inhibiting the processing or translation of the mRNA.

Designed to target mRNA, ASOs are small single-stranded coded segments complementary to the mRNA target. These synthetic molecules are generated as a complement to the coding or non-coding mRNA target region of RNA transcripts with conditions for optimal mRNA binding. ASOs are structured with a phosphorothioate backbone, and a sugar ring as a single-stranded nucleic acid fragment designed to bind to complementary mRNA molecules that encode a disease-related protein to down-regulate, modify, or restore protein expression depending on if the molecule is associated with a toxic gain of function or loss of function. Antisense oligonucleotides work by mediating degradation of the target mRNA which blocks protein expression of the target gene.

Designing ASOs requires a strong scientific and technical understanding of the molecular functionality of oligos. An important design consideration is verifying that the ASO does not have high similarity to other genes within human or animal cells to ensure off-target effects are minimized. Taking into consideration the secondary and tertiary folding of the target mRNA segment is also of pivotal importance as folding could make the mRNA sequence difficult for the ASO to access at certain locations. There are customized tools that can help with RNA structural accessibility. ASOs are often designed to target the start codon or splice site depending on whether the wanted effect is to block translation or to block splicing.

Our ASO ordering tool makes it easy for you to custom order your antisense oligonucleotides. Within the tool, you have the capability of custom naming the oligo based on your internal process needs. We offer purification as a selection, along with scale, and any 3’ or 5’ end modifications that your specific oligo requires. These end modifications can help to enhance the stability of the ASO, prolonging nuclease degradation. Additional modifications include LNA and methoxyethyl modification with the goal of increasing resistance to nucleases, increasing the melting temperature, and to adjust the affinity of the ASO for the target mRNA segment. There is a box to type in the specific sequence you would like synthesized. Refreshing the price will give updates per the specifications requested, and by clicking add to cart an option for immediate payment or a price quote may be selected. With over a decade of ASO synthesis experience, we are a trusted partner in meeting your specific needs.

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