The clinical use of CRISPR-Cas9, RNA or ASOs to treat a wide range of diseases in somatic cells has been greatly hampered by the body’s defence systems. The immune system and drug compartmentalisation at the gross and sub-cellular level result in reduced drug bioavailability.[1,2 & 3].
The Exogenix lab at the University of Greenwich has protected two intracellular drug delivery technologies that utilise the intracellular trafficking of disarmed anthrax toxin to access the cytosol.
Anthrax toxin has been detoxified and engineered to deliver siRNA, ASOs or Cas9 to target cells, giving rise to the Anthragenix technology.
This system circumvents toxicity, whilst retaining efficiency comparable to that of Nucleofection . This sets it apart from most synthetic non-viral delivery systems limited in toxicity and PK-PD by the “PEG dilemma”.
The Exogenix delivery platform can load macromolecular drugs into exosomes in situ. Exosomes are small (30-300nm) cell derived liposome-like structures which carry nucleic acids and proteins from the nucleocytosolic compartment of one cell to that of another, evading the immune system and enzymatic destruction. The Exogenix delivery platform makes it possible to load macromolecular drugs into exosomes and use them to deliver macromolecular RNA-based drugs to cells.