SS-cleavable and pH-responsive lipid-like material for gene delivery and nucleic acid delivery system
We have newly developed COATSOME® SS-series lipids for effective intracellular delivery and lower toxicity. COATSOME® SS-series contains dual sensing motifs that can respond to the intracellular environment; tertiary amines respond to an acidic compartment (endosome/lysosome) for membrane destabilization and disulfide bond that can cleave in the reductive environment (cytoplasm). These two units synergize for efficient intracellular delivery of encapsulated drugs with enhanced biosafety.
Proof of Concept
Particle formation
Serum resistance
Membrane disruption in the cells
The particle composed COATSOME® SS Series is stable in serum, hence enzymatic degradation of pDNA was prevented by encapsulation.
Also the particle composed of COATSOME® SS Series was effectively destabilized in the cytoplasmic environment.
Degradation of COATSOME® SS-OP
in vivo toxicity in comparison to a competitor lipid
Examples of application
COATSOME® SS Series enables delivery of various compounds in vivo by features of its intracellular delivery ability and biosafety. COATSOME® SS Series particles can encapsulate pDNA, siRNA, mRNA and hydrophobic low molecular weight compounds, and has been proven in delivery targeting tumor, spleen, lymph node and brain. In the following we will introduce hepatic siRNA delivery data, hepatic mRNA delivery data and lymphatic mRNA delivery data for RNA vaccine application as examples.
Hepatic delivery of siRNA
Distribution of [3H] labeled LNPSS-EC
Hepatic delivery of mRNA
Gene editing (CRISPR/Cas9)
RNA vaccine
Humoral immunity
Therapeutic anti-tumor effect
in vitro transfection of mRNA
Splenic delivery formulation
Lyophilized LNP
Feature
• Encapsulation: siRNA, mRNA, pDNA
• Efficient drug delivery into the cytoplasm of cells
• Biodegradability and low toxicity
• Controlled targeting of organs: liver, spleen, or lymph nodes
Formulations
