Delivery Platform

Silence has developed proprietary lipid-based siRNA delivery technology platforms, also known as siRNA-lipoplex technologies.

Delivery Technology

Silence has developed proprietary lipid-based siRNA delivery technology platforms, also known as siRNA-lipoplex technologies. Silence's unique platforms are based on proprietary lipid components which embed siRNA into lipid-bi-layer particles. The siRNA is combined with Silence's developed lipid moieties containing cationic lipids, co-lipids (fusogenic or stabilizing) and PEGylated lipids, form nanoparticle structures with various pharmacodynamic properties, enabling functional delivery to various cell types upon systemic administration.

Silence's sophisticated and flexible delivery technologies provide the company with unmatched potential to develop solutions for delivering RNAi molecules to a wide variety of disease tissue. This versatility positions Silence to be as a partner of choice for pharmaceutical and biotechnology companies currently working in, or seeking to enter, the RNAi field.

Silence's Formulation & Delivery Concept

Silence has developed a technology that correlates physico-chemical properties of lipoplexes with in vitro / in vivo transfection activities and aligns these correlations with in vivo organ distributions, PK & PD data in an integrated approach. Based on this integrated approach Silence has achieved the competence for an impressive and rational design of its advanced delivery systems.

Research


Silence combines its proprietary cationic lipids with a set of selected co-lipids and PEGylated lipids to create diverse lipid systems and specific siRNA formulations. This process allows the specific adjustment of the delivery system's properties towards following aspects:

  • 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

Silence's proprietary cationic lipids

Silence's delivery platform is based on its unique class of proprietary cationic lipids, such as AtuFECT01, characterized by their particular chemical structures. Instead of being focused on single-charged glycerol or amino-propane based compounds, Silence followed the idea of using multivalent cationic lipids containing a peptide based backbone and a Y-shaped lipid tail structure.

Cationic lipids

AtuFECT01: a biodegradable and multivalent cationic lipid

Silence's cationic lipids bear multiple functionalities that are essential for in vivo activity. These are amongst others:

  • 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

Delivery Systems

Silence's formulation concept covers the whole lipoplex spectrum: namely 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 behavior of siRNA / lipid formulations is mainly determined by the complex interaction between lipoplex charge / morphology / PEGylation / size and includes even non-spherical lipoplexes.

The following delivery systems are currently available for RNAi in the following target structures:

Click on the delivery systems to discover more about Silence's involvement.


Name Description
AtuPLEX® The AtuPLEX® system broadly delivers siRNA to the endothelial cells of the vascular system.
DACC The DACC system specifically delivers siRNA to vascular endothelial cells of the lung.
DBTC The DBTC system specifically delivers siRNA to hepatocytes and the hepatic vascular system of the liver parenchyma.