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.
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.
Tailored surface lipids combined with pH dependant silicon/RNA bond dissolution maximise transfection efficiency.
Versatility of particle size, surface charge and the addition of surface ligands enables passive or active cell targeting and multiple administration routes.
The structural integrity of the Silicon metalloid prevents physical collapse of the particle permitting lyophilisation whilst retaining RNA integrity.
Surface lipids and amino acids control the rate of silicon hydrolysis to only produce 100% bioabsorbable ortho silicic acid (OSA), leaving no harmful metabolites or accumulation.
A patent landscape review has shown clear freedom to operate for SiSaf’s central concept of formulating a lipid nanoparticle with hydrolysable silicon for nucleic acid delivery.
THE LIMITLESS FUTURE OF RNA THERAPEUTICS
RNA therapeutics comprise a rapidly expanding category of drugs that will change the standard of care for many genetic, metabolic and infectious diseases. These drugs are cost-effective, relatively simple to manufacture, and can target previously undruggable pathways. However, the challenges of stability, toxicity & immunogenicity are preventing many potential RNA therapies from becoming a clinical reality.
DELIVERY IS THE FUNDAMENTAL CHALLENGE
Critical to the success of RNA-based therapeutics is the delivery system that must stabilise and protect the RNA molecules from degradation, 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 their systemic survival and necessitating ultra-cold storage and transportation. The high proportion of cationic lipid used in LNPs can create toxicity when oxidised and due to the prevalence of Poly ethylene glycol (PEG), can trigger antibodies (αPEG Abs) against the polymer, which recognize PEG as foreign.
A principal constraint of LNPs is the highly restrictive patent landscape which imposes limitations on companies’ freedom to operate in RNA-based therapies.
Monday September 12, 2022
Saturday April 3, 2021
Part of the Methods in Molecular Biology book series (MIMB,volume 2282) pp 443–453
Saturday October 10, 2020
Journal of Controlled Release, Volume 326, 2020, Pages 192-202, ISSN 0168-3659,