SS-cleavable and pH-responsive Lipids (COATSOME® SS-Series)

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


• 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