Delivery platforms are key to RNA therapies as RNA molecules require delivery systems for efficient cellular uptake. Our delivery systems aid cell entry and functional delivery.
Our delivery platforms
Silence has developed proprietary lipid based RNA delivery technology platforms, also known as RNA-lipoplex technologies. The RNA molecule is combined with Silence’s developed lipid formulations containing cationic lipids, co-lipids (fusogenic or stabilising) and PEGylated lipids, to form nanoparticle structures with various pharmacodynamic properties, enabling functional delivery to various cell types upon systemic administration.
Our flexible delivery technologies provide solutions for delivering RNA molecules to a wide variety of disease tissue. This capability enables Silence to partner with pharmaceutical and biotechnology companies working in, or seeking to enter, the RNA field.
Lipoplex technology platform generates novel delivery systems
Our delivery systems combine our proprietary cationic lipids with a set of selected co-lipids and PEGylated lipids to create diverse lipid systems and specific RNA formulations. This process allows the properties of the systems to be tailored for:
- lipoplex morphology (i.e. lamellar, inverted hexagonal)
- lipoplex overall charge (cationic, neutral, anionic)
- pH dependency of lipoplex overall charge
- membrane charge density
- fusogenic properties
- shielding/interaction with serum components
- in vivo PK/circulation properties
Proprietary Cationic Lipids
Our unique class of proprietary cationic lipids, including AtuFECT, are characterised by their particular chemical structures. Instead of being focused on single-charged glycerol or amino-propane based compounds, we developed multivalent cationic lipids containing a peptide based backbone and a Y-shaped lipid tail structure.
Our cationic lipids bear multiple functionalities that are essential for in vivo activity, including:
- active and efficient siRNA loading and aggregation in lipoplexes
- sufficient protection of siRNA from degradation by nucleases
- appropriate interaction with negative charged cell surfaces
- strong interaction with endosomal membranes, membrane fusion and endosomal release of siRNA into cytoplasm
- biodegradable due to naturally occurring peptide bonds within the hydrophilic backbone
- basic fusogenic properties due to the well-balanced design between hydrophobic tails and hydrophilic head group
Core Delivery Systems
Our formulation concept covers the whole lipoplex spectrum from highly cationic to neutral and anionic lipoplexes. This approach generates a unique diversity of delivery systems, based on the conclusion that the in vivo behaviour of RNA/lipid formulations is mainly determined by the complex interaction between lipoplex charge/morphology/PEGylation/size and includes even non-spherical lipoplexes.