Developing the Caf1 polymer technology into a commercial propositionEP/T005963/1
Lead Research Organisation:
Newcastle University
Department Name: Biosciences Institute
Abstract
Pharmaceuticals have developed via three manufacturing revolutions. The first arose in the 19th century from the ability to chemically synthesise drugs previously only obtainable from natural sources (aspirin, quinine). Next in the 1970's the biotechnology revolution enabled proteins such as insulin, clotting factors or antibodies to be developed into safe widespread treatments. Currently we are in the midst of the cell therapy revolution where the ability to grow human cells outside the body is being exploited to create cell based treatments.
More generally, artificial cell culture is a widespread and rapidly expanding technology with applications in medicine, bioprocessing, crop science, drug development and clinical research. In recent years the idea of cell based therapies has moved from mere possibility to actual treatments for conditions such as leukaemia, stroke, blindness and arthritis. These require not only that cells can be grown outside the body but that they can be multiplied and modified before reintroduction into the patient. In many cases the body's immune system restricts cell therapies to autologous forms where the original cells are obtained from the patient, grown and or modified and then reintroduced. However several allogeneic treatments, where a commercial cell line is used to treat many patients, are also in development for conditions such as stroke or inherited blindness.
Much work depends upon growing stem cells which are a "raw material" that can be transformed into a wide range of tissue types for medical applications. Growing sufficient numbers of stem cells to satisfy the needs of various treatments is still a significant challenge. Cells used in research laboratories are often selected for their ability to grow rapidly and indefinitely on plastic surfaces but cells for therapy need life like environments and grow in a highly regulated manner.
Currently, cells are cultured on surfaces that largely fall into two groups; low cost, bulk materials, exemplified by plastic dishes, or high cost, low volume biological matrices which recreate the conditions found within the body and are increasingly important as more demanding or fragile cell types are used. This project seeks to use a recently developed and patented industrial process to overturn this product landscape by manufacturing engineered protein polymers with advanced cellular functions at low cost. By bridging the gap between traditional polymer science and protein biochemistry we can create a range of matrices to assist the growth of cells for many downstream applications.
The 18 month project, supported by the Cell and Gene Therapy Catapult will start by developing one lead product for use in the rapidly expanding stem cell industry. This uses simple coating of plastic surfaces by our protein polymer and has already shown significant advantages over rival technologies in stem cell culture in our hands. Independent validation will enable us to embark on its commercial exploitation to reduce costs and increase efficiency of the whole cell therapy sector.
We then intend to further demonstrate its wider applicability for work on muscle, nerve and cartilage by collaboration with leading research groups in the field and with industry. We will also test its usefulness in recreating even more realistic 3 dimensional environments for cell and tissue culture.
Finally by exploiting a recent development by us to include large protein modules within the polymer we will create a matrix which can be decorated with any number of cell modifying molecules which are found in natural extracellular environment. This offers an unprecedented opportunity to create bespoke complex cell growth environments in the "test tube"
Using both readily commercialisable products and the new intellectual property we intend to move decisively toward either spin out company or licensing agreement at the end of this project.
More generally, artificial cell culture is a widespread and rapidly expanding technology with applications in medicine, bioprocessing, crop science, drug development and clinical research. In recent years the idea of cell based therapies has moved from mere possibility to actual treatments for conditions such as leukaemia, stroke, blindness and arthritis. These require not only that cells can be grown outside the body but that they can be multiplied and modified before reintroduction into the patient. In many cases the body's immune system restricts cell therapies to autologous forms where the original cells are obtained from the patient, grown and or modified and then reintroduced. However several allogeneic treatments, where a commercial cell line is used to treat many patients, are also in development for conditions such as stroke or inherited blindness.
Much work depends upon growing stem cells which are a "raw material" that can be transformed into a wide range of tissue types for medical applications. Growing sufficient numbers of stem cells to satisfy the needs of various treatments is still a significant challenge. Cells used in research laboratories are often selected for their ability to grow rapidly and indefinitely on plastic surfaces but cells for therapy need life like environments and grow in a highly regulated manner.
Currently, cells are cultured on surfaces that largely fall into two groups; low cost, bulk materials, exemplified by plastic dishes, or high cost, low volume biological matrices which recreate the conditions found within the body and are increasingly important as more demanding or fragile cell types are used. This project seeks to use a recently developed and patented industrial process to overturn this product landscape by manufacturing engineered protein polymers with advanced cellular functions at low cost. By bridging the gap between traditional polymer science and protein biochemistry we can create a range of matrices to assist the growth of cells for many downstream applications.
The 18 month project, supported by the Cell and Gene Therapy Catapult will start by developing one lead product for use in the rapidly expanding stem cell industry. This uses simple coating of plastic surfaces by our protein polymer and has already shown significant advantages over rival technologies in stem cell culture in our hands. Independent validation will enable us to embark on its commercial exploitation to reduce costs and increase efficiency of the whole cell therapy sector.
We then intend to further demonstrate its wider applicability for work on muscle, nerve and cartilage by collaboration with leading research groups in the field and with industry. We will also test its usefulness in recreating even more realistic 3 dimensional environments for cell and tissue culture.
Finally by exploiting a recent development by us to include large protein modules within the polymer we will create a matrix which can be decorated with any number of cell modifying molecules which are found in natural extracellular environment. This offers an unprecedented opportunity to create bespoke complex cell growth environments in the "test tube"
Using both readily commercialisable products and the new intellectual property we intend to move decisively toward either spin out company or licensing agreement at the end of this project.
People |
ORCID iD |
Jeremy Lakey (Principal Investigator) |
Publications
Peters DT
(2022)
Unraveling the molecular determinants of the anti-phagocytic protein cloak of plague bacteria.
in PLoS pathogens
Le Bao C
(2022)
Spatial-Controlled Coating of Pro-Angiogenic Proteins on 3D Porous Hydrogels Guides Endothelial Cell Behavior.
in International journal of molecular sciences
Dura G
(2022)
Exploiting Meltable Protein Hydrogels to Encapsulate and Culture Cells in 3D.
in Macromolecular bioscience
Description | Execs in Business |
Amount | £30,000 (GBP) |
Organisation | United Kingdom Research and Innovation |
Department | Northern Accelerator |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2022 |
End | 06/2023 |
Description | ICURe follow on funding: FY22 round 2 Engineered Protein Polymers for Industrial Cell Culture (EPPICC) |
Amount | £240,000 (GBP) |
Organisation | Innovate UK |
Sector | Public |
Country | United Kingdom |
Start | 02/2033 |
End | 02/2033 |
Description | iCURE Cohort 15 "Engineered protein polymers for high performance, multi-purpose biomaterials" |
Amount | £40,000 (GBP) |
Funding ID | 35-15 / 520954101 |
Organisation | Set Squared Partnership |
Sector | Private |
Start | 08/2021 |
End | 03/2022 |
Description | Testing Caf1 effects on osteoprogenitor cells |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We made Caf1 proteins with BMP2 and osteopontin sequences in them and sent them to Dr Birch in Cambridge |
Collaborator Contribution | Dr Birch cultured osteoprogenitor cells on our proteins and showed that we could induce bone formation |
Impact | Peters, D. T., Waller, H., Birch, M. A., and Lakey, J. H. (2019) Engineered mosaic protein polymers; a simple route to multifunctional biomaterials, Journal of Biological Engineering 13, 54. |
Description | Testing induced pluripotent stem cell growth on engineered Caf1 surfaces |
Organisation | Cell Therapy Catapult |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Supply of engineered Caf1 coated cell culture plastic and technical advice |
Collaborator Contribution | Testing our surfaces for the ability to support iPSC culture and expansion. Comparison with existing technology used in the industry. Analysis using measures of cell number, morphology and gene expression profiles Provision of independent report of results with industrial benchmarking |
Impact | Written report comparing the behaviour of Caf1 variants with current industry standard processes. |
Start Year | 2020 |
Description | Use of Caf1 in models of vascularisation |
Organisation | Laboratory for Vascular Translational Science (LVTS) |
Country | France |
Sector | Academic/University |
PI Contribution | We supplied Caf1 specifically engineered to promote the growth of endothelial cells in 3D models |
Collaborator Contribution | They created the methods of creating the 3D models of vacularisation and the methods to analyse the results |
Impact | Int J Mol Sci . 2022 Nov 23;23(23):14604. doi: 10.3390/ijms232314604. Spatial-Controlled Coating of Pro-Angiogenic Proteins on 3D Porous Hydrogels Guides Endothelial Cell Behavior Chau Le Bao 1, Helen Waller 2, Alessandra Dellaquila 1, Daniel Peters 2, Jeremy Lakey 2, Frédéric Chaubet 1, Teresa Simon-Yarza 1 1) LVTS 2) Newcastle |
Start Year | 2021 |
Description | testing caf1 as surface for iPSC cell culture |
Organisation | Cell and Gene Therapy Catapult |
Country | United Kingdom |
Sector | Private |
PI Contribution | WE will supply engineered Caf1 proteins to test their ability to support hIPSC cell culture |
Collaborator Contribution | They will compare Caf1 with existing methods |
Impact | None yet - delayed by COVID lockdown |
Start Year | 2020 |
Company Name | MarraBio |
Description | MarraBio designs and engineers bacterial protein polymers for cell bioactivity. |
Year Established | 2022 |
Impact | None yet as it started trading on 1st Feb 2023 |
Website | https://www.marrabio.co.uk/ |