A Nanosilica-based Covid-19 Vaccine On The Horizon? Emerging vaccine delivery systems for COVID-19
Functionalised silica nanoparticles offer a potentially safe and effective alternative delivery system for DNA/RNA vaccines and may be useful in the hunt for a COVID-19 vaccine
Nanosilica for DNA and RNA delivery
Widely used in many different pharmaceutical and food situations, silica and has been proven to be safe in these various uses. As scientists looked to alternative carriers that could be adapted to encapsulate and protect nucleic acids, mesoporous silica nanoparticles (MSNs) – silica-based nanostructured materials with excellent biocompatibility and chemical stability – emerged as a suitable candidate 5, 6. In particular, nanoparticulate silica can be re-engineered to bind oligonucleotides of a range of sizes including DNA, RNA and SiRNA.
N4 Pharma is developing a novel silica nanoparticle technology for the delivery of vaccines and drugs, with a particular focus on supporting the development of cancer treatments and viral vaccines based on mRNA and pDNA. The original technology, licensed from researchers at the University of Queensland (UQ) in Australia, was developed as a nanosilica system for the delivery of a hepatitis B vaccine that would reduce the number of doses per day from three to one.
Building on this experience, the founders of N4 Pharma licensed the UQ technology and jointly developed a novel silica nanoparticle specifically designed for nucleic acid delivery has an irregular (spiky) surface structure – functionalised by coupling with polyethyleneimine (PEI). This surface simply and effectively traps and protects nucleic acids (such as mRNA/pDNA) from nuclease enzymes as it travels to the cells. Once inside the cell, the DNA/RNA is released and will result in synthesis of the foreign/target protein which will activate the immune system, leading to both a cellular and humoral immune response. The cellular response (T cells) can sense and kill infected cells and the humoral response (antibodies) will bind to the virus and (1) neutralise its capability to bind to the target cell and (2) be increasingly cleared by phagocytic mechanisms.
The new delivery system is called Nuvec®. shows the end-to-end mode of action for Nuvec® as it delivers DNA/RNA to antigen presenting cells: the Nuvec® particle carrying the DNA/RNA attaches to the cell membrane, by charge attraction, and is taken up into the cell via general and dynamin endocytosis. Once inside the endosome, the association of DNA with Nuvec changes as a consequence of the acidic environment of the endosome, releasing some DNA/RNA.
Nuvec® mode of action as it delivers DNA/RNA to antigen presenting cells.
A crucial feature of Nuvec® is that, compared to lipid-based delivery systems, it does not disrupt the cell membrane as it enters the cell and does not exhibit inflammatory response at the site of injection or any unwanted systemic side-effects. A series of studies have supported the safety, efficacy and mode of action of Nuvec® and the particle is being used in late stage pre-clinical studies.
In addition, Nuvec®’s capability to bind more than one plasmid has the potential to assist viral vector delivery. This ensures that in a multi-plasmid transfection approach, each cell will be exposed to all plasmids at the same time and can lead to less plasmid necessary to achieve the same transfection efficacy. Also during in vivo delivery of the vaccine, Nuvec® and the viral vector can work synergistically to deliver the payload.
Nuvec®’s particle will be sensed and picked up by macrophages and antigen-presenting cells. The presence of PEI will facilitate the endosomal disruption and release of nucleic acid but also presents a danger signal that will up regulate surface markers and hence attract immune cells and boost the immune response.
Delivering the vaccine
The global urgency of the COVID-19 pandemic has brought more than 25 years of research into nucleic acid-based vaccines and therapeutics into the limelight. The pharmaceutical industry, government agencies and WHO are working hard to find a COVID-19 vaccine. As researchers search for their ideal delivery platforms, safe and effective alternatives to established technologies – including emerging technologies like such as Nuvec® – can be considered.