Multifunctional nanomedicine prototypes acting as prophylactics and virus-assisted targeted drug delivery vehicle (NANOPROV)
Lead Research Organisation:
King's College London
Department Name: Pharmaceutical Sciences
Abstract
Unmet need. Viral infections are a global threat and the source of substantial social and economic burden. There is an increasing trend in the emergence and re-emergence of new viruses with high infectivity and mortality rates. Lessons learned from past pandemics, e.g. the global pandemic of SARS-CoV-2, demonstrate that a substantial amount of investment is needed to refine the science and technology to develop new early treatment antivirals. These antivirals should be based on a plug-in technology to be rapidly repurposed for treating the next fast-spreading virus and successfully managing pandemics. Approach and market. Among different technologies, pharmaceuticals based on nanoparticles show a high added value with an estimated compound annual growth rate of 22%. Protein-based nanopharmaceuticals are estimated to have a market size of $ 15 billion. NANOPROV will create novel protein-based prophylactic nanomedicines. The primary target group (> 8 million individuals in the UK alone) will be public servants and immunocompromised patients (e.g. cancer patients) and those requiring primary care.
Innovative solution and background. NANOPROV will use a plug-in nanocage technology we have patented and built upon available data regarding antiviral binding proteins. It creates proof-of-concept efficacious antiviral prophylactic nanocages for early treatment. The plug-in technology can be quickly modified using genetic engineering and repurposed to create prophylactic nanocages against a new rapidly spreading virus. The project will generate the proof of concept product for developing inhalable formulations and preclinical tests. Our plug-in nanocage technology is based on the ubiquitous iron-storage protein of life ferritin. This naturally occurring nanocage protein is biocompatible, safe and stable and has shown an acceptable safety profile for making other therapeutics, such as vaccines.
Team and environment. NANOPROV is a unique collaboration between experts in ferritin nanocages and those in antimicrobial therapeutics working at King's College London and the UK Health Security Agency (UKHSA). The Team has extensive experience developing antimicrobial products and collaborates with world-leading experts in inhalation drug delivery, formulation, and manufacturing and with biopharmaceutical companies.
Expected impact. NANOPROV will refine the science and technology for developing early treatment protein-based nanopharmaceuticals. This unique cross-fertilisation of expertise and experience will create prototype antiviral nanomedicines and technological advances for rapid repurposing to counter a fast-spreading new virus. It will generate confidence in using our nanocage technology to develop other nanomedicines, including multivalent mosaic vaccines and multivalent anti-cancer immunotherapeutics.
Innovative solution and background. NANOPROV will use a plug-in nanocage technology we have patented and built upon available data regarding antiviral binding proteins. It creates proof-of-concept efficacious antiviral prophylactic nanocages for early treatment. The plug-in technology can be quickly modified using genetic engineering and repurposed to create prophylactic nanocages against a new rapidly spreading virus. The project will generate the proof of concept product for developing inhalable formulations and preclinical tests. Our plug-in nanocage technology is based on the ubiquitous iron-storage protein of life ferritin. This naturally occurring nanocage protein is biocompatible, safe and stable and has shown an acceptable safety profile for making other therapeutics, such as vaccines.
Team and environment. NANOPROV is a unique collaboration between experts in ferritin nanocages and those in antimicrobial therapeutics working at King's College London and the UK Health Security Agency (UKHSA). The Team has extensive experience developing antimicrobial products and collaborates with world-leading experts in inhalation drug delivery, formulation, and manufacturing and with biopharmaceutical companies.
Expected impact. NANOPROV will refine the science and technology for developing early treatment protein-based nanopharmaceuticals. This unique cross-fertilisation of expertise and experience will create prototype antiviral nanomedicines and technological advances for rapid repurposing to counter a fast-spreading new virus. It will generate confidence in using our nanocage technology to develop other nanomedicines, including multivalent mosaic vaccines and multivalent anti-cancer immunotherapeutics.
Publications
Sheng Y
(2024)
A Versatile Virus-Mimetic Engineering Approach for Concurrent Protein Nanocage Surface-Functionalization and Cargo Encapsulation.
in Small (Weinheim an der Bergstrasse, Germany)
| Title | PINC Technology for using protein nanocages as platform for drug delivery and/or making multifunctional therapeutics |
| Description | We developed a new technology for assembly protein-based nanocages as a tool for drug delivery and creating multifunctional therapeutics. Using protein engineering we created precursors of protein nanocages. These precursors can be assembled into spherical shaped nanoballs after addition of a site-specific protease. |
| Type Of Material | Biological samples |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| Impact | 1. Patent application is filed. 2. We are using the technology to create pre-approved broad-spectrum antivirals. |
| URL | https://onlinelibrary.wiley.com/doi/full/10.1002/smll.202310913 |
| Description | Application of advanced computational biochemistry for protein engineering and design |
| Organisation | Technical University Berlin |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Our research team designed and create new proteins |
| Collaborator Contribution | Staff time and access to advance computational suits for training of PhD students and performing structural modeling of new proteins |
| Impact | 1. Hoang, T. N., Wu-Lu, M., Collauto, A., Hagedoorn, P. L., Alexandru, M., Henschel, M., Kordasti, S., Mroginski, M. A., Roessler, M. M., Ebrahimi, K. H.*, The [2Fe-2S] cluster of mitochondrial outer membrane protein mitoNEET has an O2-regulated nitric oxide access tunnel, FEBS LETTERS (2025) DOI:10.1002/1873-3468.15097 2. ERC synergy grant, submitted November 2025 3. MRC DPFS, to be submitted March 19th, 2025 4. Training of MSc and PhD students |
| Start Year | 2024 |
| Description | Structural studies of proteins using X-ray Crystallography and Cyro-EM |
| Organisation | IBS Grenoble |
| Country | France |
| Sector | Private |
| PI Contribution | Our team generated the background technology and protein constructs for structural studies |
| Collaborator Contribution | Our collaborator provide expertise and in-kind contribution (staff time and access to facilities) for structural studies of proteins we have created in our lab. |
| Impact | 1. Sheng, Y., Cheng, Z., Cherrier, M., Martin, L., Li, W., Lynham, S., Nicolet, Y., Ebrahimi, K. H.*, Biomimetic control of protein nanocages assembly, SMALL (2024) 2310913. 2. ERC Synergy Grant application, submitted on November 2024 |
| Start Year | 2024 |
| Title | CONTROL OF NANOCAGE SELF-ASSEMBLY |
| Description | The invention provides constructs, pharmaceutical compositions, methods of preparing a ferritin nanocage, ferritin nanocages, methods of treating or preventing a disease in a subject, and methods of raising an immune response against an antigen. Exemplary constructs include two ferritin subunits connected by a linker, wherein the linker includes a cleavage site, wherein the linker is arranged to prevent the ferritin subunits from self-assembling into a ferritin nanocage, and wherein cleavage of the linker at the cleavage site does not prevent the ferritin subunits from self-assembling into a ferritin nanocage. |
| IP Reference | WO2024110757 |
| Protection | Patent / Patent application |
| Year Protection Granted | 2024 |
| Licensed | No |
| Description | Government roundtable discussion on broad-spectrum antivirals |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Dr Ebrahimi participated in the government roundtable discussion regarding need and potentials of developing broad-spectrum antivirals to tackle future pandemics. 16-17 experts from the UK and US joined the meeting and shared their views with Dame Angela McLean (Chair; Government Chief Scientific Adviser). |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.gov.uk/government/publications/broad-spectrum-antivirals/broad-spectrum-antivirals |
| Description | Interview with news |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | This was an interview with an international magazine, Vaccine Insight, about he new Technology we developed funded by the MRC GAP Fund and published in Small Journal. We highlighted the potential of our technology for developing new multifunctional mosaic vaccines. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.insights.bio/vaccine-insights/journal/article/3268/developing-new-nanocagebased-systems-... |
