Lungs

An elegant and non-invasive route of administration directly to the key site of disease manifestation.

Number of genetically validated targets known but no current disease modifying therapies for these devastating, life threatening disorders. RNAi therapeutics directed to disease-causing, pulmonary-expressed genes represent next great frontier.

Rationale:

  • The drug will reach directly the target tissue, i.e., the lung.
  • The drug will have to pass only a single membrane barrier, of the lung epithelial cell.
  • The concentrations of plasma proteins that prevail in the respiratory epithelium are low, which are favorable conditions for this type of MNM.

In 2019, Aposense spun out the field of respiratory viral infections into SirVir


Cystic Fibrosis

Targeting the epithelial sodium channel (ENaC)

Cystic Fibrosis (CF) is a rare disease that affects around 70,000 individuals worldwide and a predicted survival age around 43 years1. It is caused by a genetic mutation that leads to mucus buildup in the lungs and pancreas1. Patients suffering from CF can have difficulty breathing and experience frequent and persistent lung infections1. In CF patients, increased ENaC activity contributes to airway dehydration and reduced mucociliary transport1. Hence, regulation of ENaC over production is recognized as a highly beneficial therapeutic target for all CFTR mutations. To date, in numerous animal models, we have shown robust and specific knock down of the ENaC expression with no signs of adverse effects.

  1. Moore PJ, Tarran R. The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis lung disease. Expert Opin Ther Targets. 2018;22(8):687-701. doi:10.1080/14728222.2018.1501361