Delivery Platform

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

delivery systems2

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

Lipoplex Technology Platform

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.

Proprietary Cationic Lipids

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.

AtuPLEX® – broad delivery to vascular endothelium

The AtuPLEX® delivery system is our most advanced lipid based siRNA formulation. The ability to deliver RNAi broadly to the vascular endothelium, resulting in substantial RNAi activity, is the most distinguished property of theAtuPLEX® delivery system. Thus AtuPLEX® technology is ideal for the development of anti-angiogenic/anti-vascular therapies.

DACC – delivery to pulmonary endothelium

The DACC system represents a novel lipid-based formulation family which delivers siRNA efficiently to the vascular endothelium of the lung. This delivery system is exceptionally well suited to address lung-specific diseases such as Pulmonary Arterial Hypertension. The DACC system has demonstrated sustained gene silencing – a single dose is sufficient to inhibit target gene expression in lungs for up to a month.

HepaPLEX – delivery to the liver

Our HepaPLEX formulation delivers siRNA primarily to the liver and has been shown to be very well tolerated. Delivery of siRNA to the liver has also been achieved by other delivery systems, but instead of merely targeting liver hepatocytes, Silence’s HepaPLEX formulations target both liver hepatocytes and vascular endothelial cells of the liver. This unique feature opens up much broader therapeutic opportunities.

Inhibition of gene expression with Silence’s delivery platforms in mice and NHPs

Our Delivery Platforms