ASOs (Antisense Oligonucleotides) are oligonucleotides that bind to complementary RNA in the target gene through base pairing, regulating its function. They are capable of inducing gene silencing.

What are the main functions of ASOs?

1. Inducing Gene Silencing: ASOs bind to target RNA and form RNA/DNA heteroduplexes, which are then recognized and degraded by endogenous RNase H, resulting in gene silencing.

2. Blocking mRNA Translation: ASOs bind to target mRNA, preventing ribosome binding and halting the translation of mRNA into the corresponding protein.

3. Alternative Splicing Studies: ASOs are designed to complement the junctions of exons and introns in target pre-mRNA sequences. The double-stranded region formed between the ASO and pre-mRNA can prevent recognition at this location, causing the exon complementary to the ASO to be skipped during pre-mRNA maturation. This allows for the study of mRNA alternative splicing.

Antisense Oligonucleotides Functions

Why are Antisense Oligonucleotides (ASOs) chemically modified?

There are multiple compelling reasons for chemically modifying ASOs, each aimed at enhancing their therapeutic efficacy and safety. Here’s a detailed look at these reasons:

Improving Stability

Unmodified ASOs are prone to rapid degradation by nucleases present in body fluids and cells. This degradation limits their antisense activity, as they don’t last long enough to effectively bind and regulate their target RNA. Chemical modifications, such as the incorporation of modified nucleobases, sugar moieties, and backbone structures, can significantly increase resistance to nucleases. This, in turn, extends their half-life and improves their stability in vivo, allowing them to perform their therapeutic functions more effectively.

Reducing Degradation Products

The degradation of unmodified ASOs often results in the formation of small fragments or degradation products. These fragments can be immunogenic, triggering unwanted immune responses or causing other side effects. Chemical modifications can reduce the production of such degradation products, minimizing the potential for adverse reactions and enhancing the overall safety profile of ASOs.

Improving Targeting

Chemical modifications can enhance the affinity of ASOs for their target RNA sequences. This means that modified ASOs can bind more tightly and specifically to their intended targets, reducing the likelihood of dissociation and increasing the precision of gene regulation.

Unmodified ASOs may exhibit nonspecific binding to non-target RNAs, which can lead to off-target effects and errors in gene regulation. Chemical modifications can reduce this nonspecific binding, ensuring that ASOs bind only to their intended targets and improving the accuracy and specificity of gene regulation.

Reducing Toxicity

Some chemical modifications can reduce the immunogenicity of ASOs, making them less likely to be recognized by the immune system. This minimization of immune recognition reduces the risk of degradation, immune responses, and potential adverse events associated with immunogenicity.

Specific chemical modifications have been designed to reduce the toxicity of ASOs in the central nervous system (CNS). For example, modifications like BNAP-AEO have been shown to decrease ASO toxicity in the CNS, making them safer and more effective for treating neurological diseases and conditions.

Optimizing Drug Properties

Chemical modifications can enhance the solubility and stability of ASOs in various formulations, making them more suitable for drug development and administration. Improved solubility ensures better dissolution and absorption, while enhanced stability prolongs shelf life and reduces the need for stringent storage conditions.

By incorporating specific chemical modifications, researchers can control the release rate and duration of ASOs in the body. This regulation allows for the optimization of therapeutic effects, ensuring that ASOs are present at therapeutic levels for the appropriate duration, thereby maximizing efficacy and minimizing side effects.

In summary, ASOs chemical modifications are crucial for enhancing their stability, reducing degradation products, improving targeting specificity, lowering toxicity, and optimizing drug properties.

Synbio Technologies | Antisense Oligonucleotides

At Synbio Technologies, weprovide high quality antisense oligonucleotides with maximum binding affinity and stability through optimized ASOs synthesis process. Various ASOs modification types are available, while the state-of-the-art methods and cutting-edge technologies, like high-performance liquid chromatography (HPLC) purification and electrospray ionization mass spectrometry (ESI-MS) ensure the highest level of purity and accuracy.We are experts in empowring nucleic acid drug research and development.