Nucleotide Delivery

Many disease states are influenced by gene regulation which affect the expression of cellular proteins that are involved in the internal workings of cells and organs. The potential to down-regulate the pathway from gene to protein could return protein expression to normal levels alleviating the symptoms of disease.

There are several methods of modulating gene expression including the use of anti-sense oligonucleotides (AS-ON), small interfering RNAs (siRNA), and micro RNAs (miRNA).  These single or double-stranded oligonucleotides prevent transcription of mRNA sequences to proteins essentially “knocking-down” production of a specific protein.

There are more than 50 RNA interfering oligonucleotides in currently in clinical development world-wide.

Delivery Challenges

Although RNA interference offers a specific approach to protein regulation, several challenges must be overcome before this technology can penetrate into mainstream medicine.

Mode of administration - most oligonucleotide therapies involve IV / subcutaneous injection or direct injection into the site of action.

The potential to down-regulate the pathway from RNA to protein by way of mRNA interference could return protein expression to normal levels alleviating the symptoms of disease.

Systemic stability - unmodified oligonucleotides have extremely short plasma half-lives and require protection from rapid in vivo degradation and elimination.

Cellular penetration - mRNA is found in the cell cytoplasm and hence oligonucleotide therapy must efficiently penetrate cellular membranes and be internalised.

Stability in pharmaceutical formulations

Aonys® Oligonucleotide Delivery

Aonys provides a highly protective environment for both native and modified oligonucleotides and allows buccal administration and absorption.  Distribution to multiple organs is rapid and sustained.

Strategy

Medesis is actively seeking partners with oligonucleotide drug candidates who wish to use the Aonys as an enabling technology.