Antisense Oligonucleotides (ASOs)

Creative Biolabs supports antisense oligonucleotides (ASOs) development and manufacturing solutions with the integrated platform of a leading CRO company. Not only do we have ready-to-use ASO products for you to choose from, but we are also committed to customizing products for you through our services.

Product Overview

ASOs are chemically modified short-chain nucleic acids that range in length from 15 to 25 nucleotides. It is dependent on RNase H to function and could specifically degrade RNA in the cytoplasm and nucleus. ASOs mostly treat diseases by silencing mRNA, inhibiting ribosome synthesis protein, and regulating RNA splicing. The mechanism of action of ASOs, as well as improvements in clinical trial design, have played major roles in accelerating clinical transformation based on ASO strategies, particularly for the treatment of multiple neurological diseases.

Fig. 1 The mechanisms of ASOs.

Case Study

Microglia express apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2), the two most potent risk factors for Alzheimer's disease. Neurodegeneration and brain homeostasis are two processes in which microglia are essential. The lack of cross-species conservation in the sequence, structure, and function of a number of microglial proteins hinders the advancement of methods for regulating the expression of particular microglial genes. Using ASOs to regulate APOE and TREM2 expression is one way to target these genes.

After four weeks, transplanted human microglia that have been exposed to ASOs targeting APOE and TREM2 exhibit reduced responses to amyloid-β plaques due to rapid transcriptional changes. ASOs that target human microglia in an AD model have the ability to alter the transcriptional patterns and in vivo responses of these cells to amyloid plaques.

Fig. 2 Representative images show activated human microglia targeting X-34-positive amyloid-β fibrils 4 weeks after APOE ASO and TREM2 ASO treatment.^1,2

Advantages of ASOs

• ASOs can be produced rapidly, within a week. The only information required is the sequence of the mRNA.
• Inhibiting mRNA expression can lead to faster and more durable clinical responses than traditional drug targeting of proteins.
• ASOs are known to accumulate in particular tissues and organs, including adipocytes, the liver, spleen, kidney, and bone marrow. There are several ways to administer them.

Creative Biolabs, one of the world's premier biotechnology companies, boasts modern equipment and an experienced workforce. Creative Biolabs' scientists can supply you with customized ASO synthesis services. We also offer a selection of ready-to-use ASO products for various disease research; please contact us to discuss your unique project or learn more about our ASO products.

References

1. Vandermeulen, Lina, et al. "Regulation of human microglial gene expression and function via RNAase-H active antisense oligonucleotides in vivo in Alzheimer's disease." Molecular Neurodegeneration 19.1 (2024): 37.
2. under Open Access license CC BY 4.0, without modification.