Antisense Oligonucleotides Therapeutics Targeting Specific Tissues or Cells

Application

Antisense oligonucleotide (ASO) therapies for the treatment of rare diseases and cancer.

Key Benefits

Novel approach to ASO therapeutics that potentially improve tissue/cell targeting capabilities.
Increases the efficacy of ASOs while decrease off-target toxicity.
Potential to treat a variety of genetic diseases such as cancer, blood disorders, and rare conditions for which there are no viable treatment options.

Market Summary

Antisense oligonucleotides (ASOs) are an emerging therapeutic modality that allows for modulating specific RNA and subsequent protein translation for many diseases. ASOs bind to target mRNA and recruit RNAse H, causing the target mRNA to be cleaved and lowering the protein levels. Although several ASOs have now been approved, they are challenging to develop, and they can exhibit off-target effects leading to limited efficacy and harmful side effects. Hence, new technologies are needed to improve the specificity of ASOs to fully realize the enormous therapeutic potential they can offer the numerous diseases without viable treatment options.

Technical Summary

Researchers at Emory have developed a potential platform technology for specific tissue targeting of ASO therapeutics. The inventors developed a liver specific ASO by using a miRNA that triggers activation of HIF1a, which is involved in a variety of human diseases as well as essential activities in healthy cells. miR-122 is a highly specific miRNA exclusively expressed in hepatocytes and makes up a large percentage of the total hepatic miRNA pool in adult mouse and humans. HIF1a is a master transcription factor that is related to diverse human diseases, such as cancer and cardiovascular diseases. However, since HIF1a is involved in a variety of cell activities and plays protective roles in wound healing and repairing injury, as well as regulating neoangiogensis and tissue vascularization, systematically inhibiting of HIF1a may lead to side effects. Therefore, conditional regulation of HIF1a in targeted tissue or cell type could be beneficial.