The POlyhedra Delivery system (PODS™) utilizes a polyhedrin protein crystal to encase and protect a co-expressed cargo protein. The PODS™ crystal is highly stable across a range of physical conditions including temperature extremes and acidity. The PODS™ crystal is broken down by alkali or exposure to proteases releasing the cargo. PODS™ crystal are suitable for stable transport of proteins at ambient temperatures and also provide a depot effect with long-release duration. PODS™ crystals are being tested for utility as vaccines and therapeutics for regeneration of damaged and diseased tissue.
PODS™ crystals viewed under scanning electron microscope and under phase contrast light microscopy. PODS™ crystals are 1-15 microns in size with a modal size of 3-5 microns.
Study Partners: Prof Andrew McCaskie, Dr. Frances Henson, Department of Surgical Orthopaedics, University of Cambridge, UK.
This study is developing a new method of treating cartilage defects that lead to osteoarthritis (OA), specifically using growth factors (GF) delivered via a PODS™ crystal. This allows sustained release of active GF, unlike other GF delivery systems. OA is a huge clinical and economic burden to the individual and healthcare provider. In the UK, 29% of adults over 45 have OA, of which 9% is severe (Arthritis Research UK) - equating to 6.5m people. The NHS musculoskeletal program budget in 2012-2013 was £4.34bn, highlighting the potential market opportunity that exists in this area. In this study we will complete the polyhedron packaging of key growth factors, test their in vitro potential to promote cartilage and synovial stem cell biology, identify a suitable hydrogel carrier for intra-articular use, test GF efficacy in in-vivo cartilage defect model and, choosing the most potent combination, test healing efficacy in a pre-clinical model. The outcome of this project will be to provide vital pre-clinical data on the efficacy of a polyhedron protein encapsulated protein to heal cartilage defects prior to first in man trials.
Study Partners: Prof Stefano Gustinich, IIT Genova, Italy
Parkinson's is a progressive neurodegenerative disease associated with damage to a specific group of nerve cells, the dopaminergic neurons, which originate in the substantia nigra region of the brain. Numerous in-vitro and animal studies have demonstrated that neurotrophic growth factors such as GDNF and CDNF are effective at restoring function in these nerves. However, for therapeutic use, the sustained delivery of these growth factors is critical for for efficacy. Several clinical trials using neurotrophic growth factors have delivered inconclusive or negative results. In each case, standard recombinant growth factors have been used and protein stability has been cited as a key limitation. PODS™ crystals containing specific neurotrophic growth factors have been developed specifically to address this limitation and provide sustained delivery. This study is assessing the utility of PODS™ crystals to deliver a sustained and effective dose of neurotrophic growth factors to the brain to control disease development using an established in-vivo model of Parkinson's disease.
Study partners: Prof Hajime Mori, Kyoto Institute of Technology, Japan
Musculoskeletal injuries and diseases are highly prevalent, accounting for around a fifth of all medical visits and impose a significant societal and economic cost on healthcare providers. Surgical orthopedic intervention is increasingly common and frequently relies on the use of implant devices and grafts to restore musculoskeletal functionality. We are conducting pre-clinical studies to determine the utility of PODS™ crystals for a specific medical indication requiring bone regeneration.
Limbal Stem Cell deficiency
Study partners: confidential
The corneal epithelium is a stratified squamous epithelium from which superficial terminal cells are eventually shed. Limbal stem cell deficiency (LSCD) results from a loss or deficiency of the stem cells in the limbus which are responsible for re-population of the corneal epithelium. This results in a breakdown of the epithelium and consequently leads to persistent epithelial defects. These include corneal conjunctivalization and neovascularization, corneal scarring, and chronic inflammation. Symptomatically, this results in loss of corneal clarity, potential vision loss, chronic pain, photophobia, and keratoplasty failure. We are conducting pre-clinical studies to evaluate the utility of PODS™ crystals to modulate the inherent population of limbal stem cells.
Study Partners: Prof Ian Goodfellow, Department of Virology, University of Cambridge, UK
Cytokines are able to modulate the immune response to infection. We are examining the utility of PODS™ crystals to reduce infectivity rates in for infectious diseases such as norovirus to provide a prophylactic and therapeutic drug to control disease outbreaks.