aMTD-ASO, The Development Of Effective Therapy For Neurodegenerative Diseases

Antisense oligonucleotides (ASOs), single-stranded and short, have high potential for therapeutic strategy for gene-specific modulation. ASO with complementary sequence to target mRNA can reduce, restore, or modify protein expression through several distinct mechanisms following binding to target mRNA. It can apply to treat a vast array of diseases.

However, there are several limiting factors for ASOs’ practical application as therapeutics. These include susceptibility to nuclease degradation, inefficient intracellular delivery to target cells following systemic administration. Intracellular delivery of ASOs is recognized as the major barrier to effective activity of ASO within the target cell.

Therefore, ASO is investigated for treatment targeting neurodegenerative diseases through direct administration by spinal injection.

To improve poor cellular uptake process, Cellivery used its Therapeuticmolecule Systemic Delivery Technology (TSDT) to improve cell-/tissue-permeability of ASOs (Figure 1). Cellivery developed advanced macromolecule transduction domain (aMTD)-fused ASO (aMTD-ASO) which can be delivered to the central nervous system through a general administration. Therapeutic agent has been developed for disease with clear animal model which is caused by single gene disorder without certain drug to facilitate process of drug development. aMTD-ASO can represent a new and valid approach to regulate the expression of diseases-related genes and will greatly be helpful for patients who are suffering from varying diseases.

Figure 1. Structure Of aMTD-ASO