Our Enabling
Technology

RNA Delivery

The Fundamental Challenge

Nucleic acid therapeutics have tremendous potential to transform the treatment of a wide range of conditions. However, this new generation of medicines relies critically on suitable delivery systems because ‘naked’ RNA is rapidly metabolised and cleared after administration. Without an appropriate carrier, it can also provoke unwanted inflammatory and immune responses.

Effective delivery technologies are therefore essential to protect therapeutic RNA against degradation, to direct it to the desired target tissues and cells, and to avoid adverse effects. Once taken up by cells, these delivery systems must also ensure efficient release of the RNA payload into the cytoplasm.

Lipid nanoparticles (LNPs) are the current mainstay and represent the most widely used delivery mechanism for RNA therapeutics in the clinic. However, they have a number of important drawbacks that limit wider application. The key challenges for current LNPs are manufacturing, stability, safety, tissue-specific targeting and transfection efficiency.

SiSaf’s proprietary Bio-Courier technology overcomes these challenges.

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 or ionisable 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 lyophilization whilst retaining RNA integrity.

   Tailored surface lipids combined with pH dependant silicon/RNA bond dissolution maximize 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.

Manufacturing

Unlike conventional LNPs, Bio-Courier can be manufactured ‘empty’ and quickly loaded with any desired RNA therapeutic at the point of use. This eliminates the need for ultracold chain distribution and overcomes other issues due to RNA instability.

 By separating carrier manufacture from API loading, Bio-Courier technology can extend global accessibility to regions where end-to-end ultracold chain distribution is not feasible and it can reduce the environmental impact associated with ultracold transport and storage.

The modular nature of Bio-Courier also opens up new possibilities in rare disease treatments and personalized RNA medicine, as it permits the on-demand preparation of customized RNA-loaded nanoparticles on any scale at the point of use.

Safety

PEGylated lipids are an essential structural and functional component of LNPs but they can elicit unwanted immune responses, compromising both safety and efficacy.

In Bio-Courier, the stabilizing effect of the silicon component removes the need for PEGylation without introducing any additional safety issues.

  The hydrolysable silicon component of Bio-Courier particles is designed to degrade in vivo to 100% biocompatible orthosilicic acid, which is bioabsorbable and has no known safety concerns.

Targeting

Targeting of specific tissues or cell types is extremely challenging with standard LNPs due to their strong tendency to accumulate in the liver. In contrast, Bio-Courier formulations can readily be fine-tuned for RNA delivery to the desired site of action.

    In a mouse model of Osteopetrosis type 2 (ADO2), Bio-Courier achieved optimal delivery of siRNA targeting the mutant Clcn7 allele to femur, resulting in the rescue of the bone phenotyope.

Publications