Overview

POlyhedra Delivery System (PODS®) is, in effect, a protein depot formulation technology. This enables sustained therapeutic protein delivery. PODS® achieves this by utilizing a specific polyhedrin protein crystal to encase and protect the cargo protein. This PODS® crystal is highly stable across a range of physical conditions including temperature extremes and acidity. The crystals are also UV protective. The PODS® crystal can be broken down either by alkali or exposure to proteases releasing the cargo. PODS® crystals are suitable for stable transport of proteins at ambient temperatures and also provide a protein depot formulation with long-release duration. Therefore, PODS® crystals are ideal for therapeutic protein delivery. Cell Guidance Systems is collaborating with multiple groups to test the utility of PODS® to deliver protein therapeutics for regeneration of damaged and diseased tissue. 

PODS crystals SEMPODS crystals phase contrast

PODS® crystals viewed under a scanning electron microscope and under phase contrast light microscopy. PODS® crystals are 0.3-7 microns in size with a modal size of 1-2 microns.

Osteoarthritis  

Study Partners: Prof Andrew McCaskie, Dr Frances Henson, University of Cambridge, UK. 

Osteoarthritis is a major clinical and economic burden. In the UK, for example, 29% of adults over 45 have OA, of which 9% is severe (Arthritis Research UK). This is caused by damage to the cartilage tissue that protects the ends of bones in joints. Once this tissue is damaged, the joint becomes painful. Eventually, the joint may need to be replaced with a prosthetic. Surprisingly, there are no approved therapies which can slow down the progression of osteoarthritis. Our work with Cambridge University is developing a new method to treat the cartilage surface defects that lead to osteoarthritis, using growth factors delivered via PODS® crystals.    In this study, we have tested specific PODS® growth factors, both in vitro and in-vivo for their potential to promote cartilage surface defect repair. This project, which is expected to finish in 2019, will provide vital pre-clinical data on the efficacy of PODS® growth factors to heal cartilage surface defects prior to first in man trials.

Parkinson's Disease

Study Partners: Dr Susan Duty, Kings College London

Parkinson's disease (PD) 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 and extend up to the striatum. It affects about 1% of individuals age over 55. Currently available drugs alleviate symptoms, but there are no drugs for PD that can slow the overall progression of the disease.  Numerous in-vitro and animal studies have demonstrated that neurotrophic growth factors such as GDNF and CDNF are neuroprotective and effective at restoring function in mouse models of disease. However, for therapeutic use, the sustained delivery of these therapeutic proteins is critical for efficacy. Several clinical trials using neurotrophic growth factors have delivered disappointing results. In each case, standard soluble growth factors have been used in previous trials and protein stability has been cited as a key limitation. PODS® crystals containing specific neurotrophic growth factors have been developed specifically for therapeutic protein delivery to address this limitation and provide sustained delivery. This study which commenced in February 2019 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. 

Bone Regeneration

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 orthopaedic 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.

Age-Related Macular Degeneration

Study partners: Dr Pert Baranov and Dr Julia Oswald, Schepens Eye Institute

Loss of cells lining the inside of the eye due to disease leads to loss of central vision. Replacing these cells with iPSC-derived cells has the potential to reverse the effects of AMD.  Researchers at Schepens Eye Institite at Harvard University have been using PODS® containing BDNF and GDNF to improve the quality of iPSC-derived retinal organoids. They found that using PODS® produced higher quality organoids - possibly because this requires fewer interventions. Petr and Julia are dissociating the cells prior to injecting into eyes along with PODS® proteins to promote implanted cell survival and engraftment.

Cochlear Implant Integration

Study partners: Dr Aki Matsuoka, Northwestern University

Cochlear Implants are now widely used to restore hearing loss. The performance of the implant depends, in part, on the level of integration of the implant with neuronal cells lining the inner ear which conduct nerve signals to auditory regions of the brain. Dr Matsuoka is exploring the use of PODS® containing neurotrophic growth factors to coat the cochlear implant. It is anticipated that these will establish a gradient that will attract neuronal cells resulting in improved cochlear implant integration.

Infection 

Study Partners: Prof Ian Goodfellow, 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 for infectious diseases such as norovirus to provide a prophylactic and therapeutic drug to control disease outbreaks.

If you are interested in exploring PODS® for therapeutic protein delivery and would like to collaborate, please get in touch