Predictive bioinformatic platforms for direct cellular reprogramming: Mogrify Ltd (final part)
Since its launch, Mogrify Ltd has started several projects on different therapeutic areas of regenerative medicine, which have made use of the prediction results from its computation platform Mogrify. In this blog post, I am going to present to you what I have found from the company’s website. (I am not sponsored by them, just looking.)
Application of the prediction from MOGRIFY
Through its wholly-owned subsidiary, Chondrogenix, Mogrify Ltd has stepped into the therapeutic area of musculoskeletal diseases such as osteoarthritis. The algorithm platform MOGRIFY identified a cocktail of transcription factors for the company, Chondrogenix, to convert, in a culture dish, different starting cell types from diseased patients, into functional chondrocytes that are capable of forming cartilage. Musculoskeletal diseases are usually caused by bone or cartilage defects. This technology paved the way for them to write an application request to the regulators to enhance the FDA-approved Autologous Chondrocyte Implantation (ACI) therapy, and to create additional reprogramming therapies using cells from donors (allogenic reprogramming therapy) or by direct cell conversion in living organisms (in vivo reprogramming therapy). Chondrogenix received two phases of funding from SBRI Healthcare for this project.1,2
Mogrify Ltd is also using its computational platform to predict combinations of transcription factors to induce conversion of one cell type to another in order to produce proteins which are not produced sufficiently well by existing production systems. The resulting target cell types could provide researchers with improved access to important proteins found in human cell types that are difficult to obtain, and allow for more efficient antibody production methods for biologic drugs. This exploratory research is done with the collaboration of the MRC’s Laboratory of Molecular Biology (MRC-LMB) in Cambridge.3
In fact, Mogrify Ltd also collaborates with MRC-LMB to improve the MOGRIFY cell reprogramming platform itself. The enhanced version, MOGRIFY V2, incorporates data from next-generation sequencing and single-cell RNA sequencing into the algorithm to enhance the quality and accuracy of transcription factor predictions and cell conversion efficacy.4
Furthermore, Mogrify Ltd is also involved in allogeneic (using cells from a donor who is not the patient) T-cell immunotherapy for inflammatory and autoimmune diseases, by collaborating with Sangamo Therapeutics, a genomic medicine company in the US. Mogrify is responsible for the discovery and optimisation of the cell conversion technology from induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) to regulatory T cells (Tregs). Sangamo expects to then use its technology and therapeutic development capabilities to transform these Tregs cells into ready to use allogeneic therapy candidates for the treatment of inflammatory and autoimmune diseases. The resulting collaboration will hopefully accelerate the development of scalable and accessible CAR-Treg cell therapies so that the treatments can be delivered more rapidly, in a more cost-effective way to a larger patient population.5
Financial Support
Since its launch in February 2019, Mogrify Ltd has attracted investments from strategic corporate investors to strengthen its business. According to a press release of the company in May this year, Mogrify Ltd has raised a total of US$33 million from seed funding and two rounds of Series A financing. The investors include Ahren Innovation Capital, 24Haymarket, Dr. Darrin M. Disley, OBE (CEO of Mogrify Ltd), Parkwalk Advisors, Astellas Venture Management, Dr Jonathan Milner (co-founder of Abcam PLC), and the University of Bristol Enterprise Fund III.6
In March 2019, Mogrify Ltd was awarded $555,000 (£420,000) from Innovate UK, a UK innovation agency, on a data-driven cell conversions project to produce cell therapies with potential applications in wound healing and oncology immunotherapy.7
Moreover, Chondrogenix (the subsidiary of Mogrify Ltd) received two rounds of funding from SBRI Healthcare, an NHS England initiative, championed by the Academic Health Science Networks (AHSNs). These funds were awarded for the purpose of generating a safe, efficient and scalable source of cartilage cells for the treatment of cartilage defects, osteoarthritis and other musculoskeletal conditions.1,2
Conclusion
From the above information, it is obvious that Mogrify Ltd has ambition to develop and scale up reprogramming of cells for many autologous and allogeneic cell therapies, as well as to create in vivo reprogramming therapies (direct cell conversion in living organisms).1-3,5 The two software platforms developed by the company no doubt speed up the process of direct cellular reprogramming, by using algorithms based on the big data already available in public repositories instead of performing trial and error experimentally. With the financial support it has got so far, I have no doubt that the company, in the near future, can meet its target of producing stable reprogrammed cells at scale for some areas of cell therapies. However, the company needs to overcome some challenges when it comes to clinically applying its reprogrammed cells.
The hurdles include the safety issues regarding the components suggested by the software platforms for cell conversion. There is a possibility that some biological factors such as cMYC, when overexpressed, can cause tumour growth.10,11 The method to deliver biological factors safely is also a concern. Engineered viruses constructed to deliver transcription factors may integrate into a DNA region of target cells and cause a tumour later. In addition, the recipient’s immunity against the reprogrammed cells also needs to be addressed. These challenges, though, are also faced by other biotech companies focusing on regenerative medicine.
Besides the above-mentioned issues, I am eager to see the reports on the experiments, which apply the prediction from MOGRIFY8 and epiMOGRIFY9, to be published soon. I am also expecting Mogrify Ltd will merge the two software platforms into a single platform with synergistic power.
References
1. Mogrify subsidiary Chondrogenix secures funding from SBRI Healthcare to advance regenerative cartilage therapy to the clinic. Mogrify Ltd press release, 1st April, 2019. https://mogrify.co.uk/mogrify-subsidiary-chondrogenix-secures-funding-from-sbri-healthcare-to-advance-regenerative-cartilage-therapy-to-the-clinic/
2. Mogrify awarded $1.1M additional funding from SBRI Healthcare. Mogrify Ltd press release, 28th January, 2020. https://mogrify.co.uk/mogrify-awarded-1-1m-additional-funding-from-sbri-healthcare/
3. Mogrify enters research collaboration with the MRC Laboratory of Molecular Biology. Mogrify Ltd press release, 11th January, 2021. https://mogrify.co.uk/mogrify-enters-research-collaboration-with-the-mrc-laboratory-of-molecular-biology/
4. Mogrify solidifies IP position surrounding core technology and expands platform algorithm to enhance cell conversion. Mogrify Ltd press release, 17th December, 2020. https://mogrify.co.uk/mogrify-solidifies-ip-position-surrounding-core-technology-and-expands-platform-algorithm-to-enhance-cell-conversion/
5. Mogrify and Sangamo announce collaboration and exclusive license agreement for Mogrify’s iPSC- and ESC-derived regulatory T cells. Mogrify Ltd press release, 21st April, 2020. https://mogrify.co.uk/mogrify-and-sangamo-announce-collaboration-and-exclusive-license-agreement-for-mogrifys-ipsc-and-esc-derived-regulatory-t-cells/
6. Mogrify completes Series A financing totalling $33 million USD. Mogrify Ltd press release, 4th May, 2021. https://mogrify.co.uk/mogrify-completes-series-a-financing-totaling-33-million-usd/
7. Mogrify awarded $555,000 USD (£420,000 GBP) Innovate UK funding to accelerate regenerative cell therapies. Mogrify Ltd press release, 18th March, 2019. https://mogrify.co.uk/mogrify-awarded-555000-usd-420000-gbp-innovate-uk-funding-to-accelerate-regenerative-cell-therapies/
8. O.J.L. Rackham, J. Firas, and H. Fang, et al. A predictive computational framework for direct reprogramming between human cell types. Nature Genetics, March 2016, Vol. 48, No. 3.
9. U.S. Kamaraj, J. Chen, and K. Katwadi, et al. EpiMogrify models H3K4me3 data to identify signaling molecules that improve cell fate control and maintenance. Cell Systems, 2020, 11, 509–522, November 18.
10. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006;126:663–676.
11. Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer. 2008;8:976–990
Since its launch, Mogrify Ltd has started several projects on different therapeutic areas of regenerative medicine, which have made use of the prediction results from its computation platform Mogrify. In this blog post, I am going to present to you what I have found from the company’s website. (I am not sponsored by them, just looking.)
Application of the prediction from MOGRIFY
Through its wholly-owned subsidiary, Chondrogenix, Mogrify Ltd has stepped into the therapeutic area of musculoskeletal diseases such as osteoarthritis. The algorithm platform MOGRIFY identified a cocktail of transcription factors for the company, Chondrogenix, to convert, in a culture dish, different starting cell types from diseased patients, into functional chondrocytes that are capable of forming cartilage. Musculoskeletal diseases are usually caused by bone or cartilage defects. This technology paved the way for them to write an application request to the regulators to enhance the FDA-approved Autologous Chondrocyte Implantation (ACI) therapy, and to create additional reprogramming therapies using cells from donors (allogenic reprogramming therapy) or by direct cell conversion in living organisms (in vivo reprogramming therapy). Chondrogenix received two phases of funding from SBRI Healthcare for this project.1,2
Mogrify Ltd is also using its computational platform to predict combinations of transcription factors to induce conversion of one cell type to another in order to produce proteins which are not produced sufficiently well by existing production systems. The resulting target cell types could provide researchers with improved access to important proteins found in human cell types that are difficult to obtain, and allow for more efficient antibody production methods for biologic drugs. This exploratory research is done with the collaboration of the MRC’s Laboratory of Molecular Biology (MRC-LMB) in Cambridge.3
In fact, Mogrify Ltd also collaborates with MRC-LMB to improve the MOGRIFY cell reprogramming platform itself. The enhanced version, MOGRIFY V2, incorporates data from next-generation sequencing and single-cell RNA sequencing into the algorithm to enhance the quality and accuracy of transcription factor predictions and cell conversion efficacy.4
Furthermore, Mogrify Ltd is also involved in allogeneic (using cells from a donor who is not the patient) T-cell immunotherapy for inflammatory and autoimmune diseases, by collaborating with Sangamo Therapeutics, a genomic medicine company in the US. Mogrify is responsible for the discovery and optimisation of the cell conversion technology from induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) to regulatory T cells (Tregs). Sangamo expects to then use its technology and therapeutic development capabilities to transform these Tregs cells into ready to use allogeneic therapy candidates for the treatment of inflammatory and autoimmune diseases. The resulting collaboration will hopefully accelerate the development of scalable and accessible CAR-Treg cell therapies so that the treatments can be delivered more rapidly, in a more cost-effective way to a larger patient population.5
Financial Support
Since its launch in February 2019, Mogrify Ltd has attracted investments from strategic corporate investors to strengthen its business. According to a press release of the company in May this year, Mogrify Ltd has raised a total of US$33 million from seed funding and two rounds of Series A financing. The investors include Ahren Innovation Capital, 24Haymarket, Dr. Darrin M. Disley, OBE (CEO of Mogrify Ltd), Parkwalk Advisors, Astellas Venture Management, Dr Jonathan Milner (co-founder of Abcam PLC), and the University of Bristol Enterprise Fund III.6
In March 2019, Mogrify Ltd was awarded $555,000 (£420,000) from Innovate UK, a UK innovation agency, on a data-driven cell conversions project to produce cell therapies with potential applications in wound healing and oncology immunotherapy.7
Moreover, Chondrogenix (the subsidiary of Mogrify Ltd) received two rounds of funding from SBRI Healthcare, an NHS England initiative, championed by the Academic Health Science Networks (AHSNs). These funds were awarded for the purpose of generating a safe, efficient and scalable source of cartilage cells for the treatment of cartilage defects, osteoarthritis and other musculoskeletal conditions.1,2
Conclusion
From the above information, it is obvious that Mogrify Ltd has ambition to develop and scale up reprogramming of cells for many autologous and allogeneic cell therapies, as well as to create in vivo reprogramming therapies (direct cell conversion in living organisms).1-3,5 The two software platforms developed by the company no doubt speed up the process of direct cellular reprogramming, by using algorithms based on the big data already available in public repositories instead of performing trial and error experimentally. With the financial support it has got so far, I have no doubt that the company, in the near future, can meet its target of producing stable reprogrammed cells at scale for some areas of cell therapies. However, the company needs to overcome some challenges when it comes to clinically applying its reprogrammed cells.
The hurdles include the safety issues regarding the components suggested by the software platforms for cell conversion. There is a possibility that some biological factors such as cMYC, when overexpressed, can cause tumour growth.10,11 The method to deliver biological factors safely is also a concern. Engineered viruses constructed to deliver transcription factors may integrate into a DNA region of target cells and cause a tumour later. In addition, the recipient’s immunity against the reprogrammed cells also needs to be addressed. These challenges, though, are also faced by other biotech companies focusing on regenerative medicine.
Besides the above-mentioned issues, I am eager to see the reports on the experiments, which apply the prediction from MOGRIFY8 and epiMOGRIFY9, to be published soon. I am also expecting Mogrify Ltd will merge the two software platforms into a single platform with synergistic power.
References
1. Mogrify subsidiary Chondrogenix secures funding from SBRI Healthcare to advance regenerative cartilage therapy to the clinic. Mogrify Ltd press release, 1st April, 2019. https://mogrify.co.uk/mogrify-subsidiary-chondrogenix-secures-funding-from-sbri-healthcare-to-advance-regenerative-cartilage-therapy-to-the-clinic/
2. Mogrify awarded $1.1M additional funding from SBRI Healthcare. Mogrify Ltd press release, 28th January, 2020. https://mogrify.co.uk/mogrify-awarded-1-1m-additional-funding-from-sbri-healthcare/
3. Mogrify enters research collaboration with the MRC Laboratory of Molecular Biology. Mogrify Ltd press release, 11th January, 2021. https://mogrify.co.uk/mogrify-enters-research-collaboration-with-the-mrc-laboratory-of-molecular-biology/
4. Mogrify solidifies IP position surrounding core technology and expands platform algorithm to enhance cell conversion. Mogrify Ltd press release, 17th December, 2020. https://mogrify.co.uk/mogrify-solidifies-ip-position-surrounding-core-technology-and-expands-platform-algorithm-to-enhance-cell-conversion/
5. Mogrify and Sangamo announce collaboration and exclusive license agreement for Mogrify’s iPSC- and ESC-derived regulatory T cells. Mogrify Ltd press release, 21st April, 2020. https://mogrify.co.uk/mogrify-and-sangamo-announce-collaboration-and-exclusive-license-agreement-for-mogrifys-ipsc-and-esc-derived-regulatory-t-cells/
6. Mogrify completes Series A financing totalling $33 million USD. Mogrify Ltd press release, 4th May, 2021. https://mogrify.co.uk/mogrify-completes-series-a-financing-totaling-33-million-usd/
7. Mogrify awarded $555,000 USD (£420,000 GBP) Innovate UK funding to accelerate regenerative cell therapies. Mogrify Ltd press release, 18th March, 2019. https://mogrify.co.uk/mogrify-awarded-555000-usd-420000-gbp-innovate-uk-funding-to-accelerate-regenerative-cell-therapies/
8. O.J.L. Rackham, J. Firas, and H. Fang, et al. A predictive computational framework for direct reprogramming between human cell types. Nature Genetics, March 2016, Vol. 48, No. 3.
9. U.S. Kamaraj, J. Chen, and K. Katwadi, et al. EpiMogrify models H3K4me3 data to identify signaling molecules that improve cell fate control and maintenance. Cell Systems, 2020, 11, 509–522, November 18.
10. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006;126:663–676.
11. Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer. 2008;8:976–990
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