Science
SiSaf’s Bio-Courier technology combines a proprietary bioabsorbable silicon matrix with surface lipids and amino acids, a structure that addresses several of the major limitations and concerns associated with lipid nanoparticles to deliver RNA therapeutics.
Silicon’s durable electrostatic potential helps bind and stabilise RNA reducing the need for potentially toxic cationic lipids and averting the risk of premature detachment of RNA.
The high structural integrity of the silicon metalloid matrix prevents collapse on freeze drying and reduces the need for PEGylation, a key step to avoid the need for ultra-cold supply chain storage.


Bio-Courier® Technology
The Solution
SiSaf’s Bio-Courier technology addresses the challenges of lipid nanoparticles by stabilizing both lipids and RNA through a bioabsorbable silicon matrix.
Silicon’s positive charge and high ζ-potential electrostatically bind and condense RNA preventing the premature disassociation of RNA and reducing the reliance on cationic lipids.
High volumes of tightly condensed RNA are electrostatically bonded to the silicon matrix, protecting them from hydrolysis to prolong their systemic survival.
The structural integrity of the Silicon metalloid prevents physical collapse of the particle permitting lyophilisation whilst retaining RNA integrity.
Tailored surface lipids combined with pH dependant silicon/RNA bond dissolution maximise transfection efficiency.
The versatility of particle size, surface charge and the addition of surface ligands enable passive or active cell targeting and multiple administration routes.
RNA Delivery
The Fundamental Challenge
Critical to the success of RNA-based therapeutics is the delivery system. It needs to stabilise and protect the RNA molecules from degradation, and it needs to ensure delivery to the target cell’s cytoplasm in sufficient quantities to elicit the desired cellular response with little or no adverse effects or accumulation.
Lipid nanoparticles (LNPs), the current mainstay, are fragile and can allow RNA to detach as their electrostatic potential deteriorates, limiting systemic survival and necessitating ultra-cold storage and transportation.
The high proportion of cationic lipids used in LNPs can create toxicity when oxidised and the prevalence of polyethylene glycol (PEG) can trigger antibodies (αPEG Abs), which recognize PEG as foreign.

RNA Delivery
The Fundamental Challenge
Critical to the success of RNA-based therapeutics is the delivery system. It needs to stabilise and protect the RNA molecules from degradation, and it needs to ensure delivery to the target cell’s cytoplasm in sufficient quantities to elicit the desired cellular response with little or no adverse effects or accumulation.
Lipid nanoparticles (LNPs), the current mainstay, are fragile and can allow RNA to detach as their electrostatic potential deteriorates, limiting systemic survival and necessitating ultra-cold storage and transportation.
The high proportion of cationic lipids used in LNPs can create toxicity when oxidised and the prevalence of polyethylene glycol (PEG) can trigger antibodies (αPEG Abs), which recognize PEG as foreign.

Bio-Courier® Technology
The Solution
SiSaf’s Bio-Courier technology addresses the challenges of lipid nanoparticles by stabilizing both lipids and RNA through a bioabsorbable silicon matrix
Silicon’s positive charge and high ζ-potential electrostatically bind and condense RNA preventing the premature disassociation of RNA and reducing the reliance on cationic lipids.
High volumes of tightly condensed RNA are electrostatically bonded to the silicon matrix, protecting them from hydrolysis to prolong their systemic survival.
The structural integrity of the Silicon metalloid prevents physical collapse of the particle permitting lyophilisation whilst retaining RNA integrity.
Tailored surface lipids combined with pH dependant silicon/RNA bond dissolution maximise transfection efficiency.
The versatility of particle size, surface charge and the addition of surface ligands enable passive or active cell targeting and multiple administration routes.

Bio-Courier vs LNP
LNP
Bio-Courier


STABILITY
Cationic lipids lose charge
Silicon high zeta potential
The use of the positively charged silicon matrix to bind and stabilise the RNA payload reduces the need for cationic lipids, avoiding the risk for premature leakage of RNA from the nanoparticles as the positive charge from the lipids decays.
COLD CHAIN
Require ultra cold chain
Storage stability at room temperature
The structural integrity of the Silicon metalloid prevents physical collapse of the particle on lyophilisation, a key step to avoid the need for ultra-cold storage. Bio-Courier have been shown to be stable at room temperature for several months.
TOXICITY
Excess cationic lipids can be toxic
80% less cationic lipids
Cationic lipids can induce cytotoxicity. The significnatly reduced amount of cationic lipids in silicon stabilized lipid nanoparticles reduces the risk of cytotoxicity.
Bio-Couriers have been shown to be non-toxic and safe.
IMMUNOGENICITY
Risk of antibody formation against PEG
Reduced PEG
Stabilization of the lipid coating via the high structural integrity of the silicon matrix core avoids the need for PEGylation to achieve structural stability.
This reduces the risk of an immune response against PEG.
CONTROLLED RELEASE
Limited control of RNA release
Tuneable carrier biodegradation
Surface lipids and amino acids coating the silicon core control the rate of silicon hydrolysis, and they can be customized to provide controlled release and targeting of specific cells and tissues.
Bio-Courier vs LNP
LNP
Bio-Courier


Stability
LNP
Bio-Courier
Cationic lipids lose charge
Silicon high zeta potential
The use of the positively charged silicon matrix to bind and stabilise the RNA payload reduces the need for cationic lipids, avoiding the risk for premature leakage of RNA from the nanoparticles as the positive charge from the lipids decays.
Cold Chain
LNP
Bio-Courier
Require ultra cold chain
Storage stability at room temperature
Toxicity
LNP
Bio-Courier
Excess cationic lipids can be toxic
80% less cationic lipids
Bio-Couriers have been shown to be non-toxic and safe.
Immunogenicity
LNP
Bio-Courier
Risk of antibody formation to PEG
Reduced PEG
This reduces the risk of an immune response against PEG.
Controlled Release
LNP
Bio-Courier
Limited control of RNA release
Tuneable carrier biodegradation
Publications
Delivery of siRNA to the Eye
2021
In: Ditzel, H.J., Tuttolomondo, M., Kauppinen, S. (eds) Design and Delivery of SiRNA Therapeutics. Methods in Molecular Biology, vol 2282. Humana, New York, NY, pp 443–453
Topical siRNA delivery to the cornea and anterior eye by hybrid silicon-lipid nanoparticles
October 2020
Journal of Controlled Release, Volume 326, 2020, pp 192-202
Effective Small Interfering RNA Therapy to Treat CLCN7-dependent Autosomal Dominant Osteopetrosis Type 2
January 2015
Molecular Therapy – Nucleic Acids (2015) 4, e248
Nanotechnology approaches to solving the problems of poorly water-soluble drugs
August 2005
Drug Discovery World, Summer 2005
High Yield Incorporation of Plasmid DNA within Liposomes: Effect on DNA Integrity and Transfection Efficiency
Gregory Gregoriadis, Roghieh Saffie & Stephen Hart
1996
Journal of Drug Targeting, 3:6, 469-475