Professor
Zoltán
Kis
(he/him)
School of Chemical, Materials and Biological Engineering
Professor of Bioprocess Engineering
z.kis@sheffield.ac.uk
G58 , Sir Robert Hadfield Building
Full contact details
Professor Zoltán Kis
G58
Sir Robert Hadfield Building
School of Chemical, Materials and Biological Engineering
G58
Sir Robert Hadfield Building
Mappin Street
Sheffield
S1 3JD
- Profile
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I am a Professor of Bioprocess Engineering in the School of Chemical, Materials and Biological Engineering at the University of Sheffield, and an Honorary Lecturer at the Department of Chemical Engineering, Imperial College London. I am also a co-founder of RNA Forge Ltd, which provides RNA analytical services and manufacturing, and of Simulenta Ltd, a bioprocess modelling consultancy.
I am leading a multidisciplinary team that is innovating and digitalising RNA vaccine and therapeutics production platform technologies. My work is addressing the challenges of producing large volumes of RNA-based vaccines and therapeutics, rapidly, at high quality and at low cost in a disease-agnostic manner.
I previously worked as a Research Associate in the Future Vaccine Manufacturing Hub at Imperial College London. I obtained my Ph.D. in Bioengineering from Imperial College London, UK, hold an M.Sc. in Applied Biotechnology and a B.Eng. in Chemical with Biochemical Engineering.
- Research interests
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Our exciting research combines experimental and computational modelling techniques to innovate RNA vaccine and therapeutics production multi-product platform processes. On the experimental front, we are developing, intensifying and scaling up continuous mRNA enzymatic synthesis, purification and formulation processes, alongside developing bespoke manufacturing equipment. Our modelling work streamlines process development and deploys software-based sensors and digital twins for monitoring and automating multi-product mRNA manufacturing. Our work is embedded into the Quality-by-Digital-Design framework and follows techno-economic considerations. Our efforts will enable the rapid development and mass manufacturing of high-quality mRNA vaccines/therapeutics at low costs against a wide range of diseases.
Key research areas include:
- Experimental mRNA vaccine and RNA therapeutics manufacturing process development: process intensification, continuous manufacturing and scale-up.
- Development and optimisation of continuous in vitro transcription (IVT) reaction for mRNA synthesis, continuous mRNA downstream purification processes based on continuous chromatography and tangential flow filtration unit operations, as well as continuous LNP formulation unit operations.
- Development of new unit operations and design of process equipment for mRNA manufacturing.
- Process digitalisation: development of soft sensors and digital twins to monitor and control the manufacturing of RNA vaccines, RNA therapeutics and other biopharmaceuticals.
- Techno-economic modelling for reducing the costs, increasing production rates and increasing production volumes of RNA vaccines, RNA therapeutics and other biopharmaceuticals.
- Quality by Digital Design for consistently ensuring product quality, support scale-up, technology transfer, and for accelerating the regulatory approval process.
- Manufacturing processes for self-amplifying RNA (saRNA) and circular RNA (circRNA), from in vitro transcription (IVT) to purification by chromatography and tangential flow filtration, and lipid nanoparticle (LNP) formulation.
- Life-cycle assessment of the environmental impacts of mRNA vaccine and therapeutics manufacturing.
- Publications
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Journal articles
- In vitro transcription for RNA vaccines and therapeutics: a quality-by-design perspective on manufacturability. Biotechnology Advances, 93. View this article in WRRO
- Integrated in vitro transcription and oligo-dT affinity chromatography enable multi-cycle reagent recycling for mRNA manufacturing. Molecular Therapy Nucleic Acids, 37(4). View this article in WRRO
- A soft sensor based on pH for real-time monitoring of mRNA medicine production. Digital Discovery, 5(7), 2899-2914. View this article in WRRO
- Analysis of mRNA multimerisation (aggregation) using non-denaturing ion-pair reversed-phase liquid chromatography. Journal of Chromatography A, 1769. View this article in WRRO
- Editorial: In vitro transcription (IVT) reaction – the gateway to new therapeutic modalities. Frontiers in Molecular Biosciences, 12. View this article in WRRO
- Advancing continuous encapsulation and purification of mRNA vaccines and therapeutics. European Journal of Pharmaceutical Sciences, 212. View this article in WRRO
- Overcoming mRNA medicine supply hurdles: distributed, continuous and multi-product mRNA manufacturing in a box at high quality and low cost. Cell and Gene Therapy Insights, 11(5), 605-620. View this article in WRRO
- Mass spectrometry-based mRNA sequence mapping via complementary RNase digests and bespoke visualisation tools. The Analyst, 150(5), 1012-1021. View this article in WRRO
- Bacteriophage RNA polymerases: catalysts for mRNA vaccines and therapeutics. Frontiers in Molecular Biosciences, 11. View this article in WRRO
- An experimental and modeling approach to study tangential flow filtration performance for mRNA drug substance purification. Biotechnology Journal, 19(11). View this article in WRRO
- Advancing mRNA production through platform and continuous process development. Nucleic Acid Insights, 1(8), 301–308-301–308.
- Quality by design for mRNA platform purification based on continuous oligo-dT chromatography. Molecular Therapy - Nucleic Acids, 35(4). View this article in WRRO
- Bioprocessing 4.0: a pragmatic review and future perspectives. Digital Discovery, 3(9), 1662-1681. View this article in WRRO
- Quality by Digital Design for Developing Platform RNA Vaccine and Therapeutic Manufacturing Processes. Methods Mol Biol, 2786, 339-364. View this article in WRRO
- Quality by design framework applied to GMMA purification. The AAPS Journal, 26(2). View this article in WRRO
- Engineering an Escherichia coli based in vivo mRNA manufacturing platform. Biotechnology and Bioengineering, 121(6), 1912-1926. View this article in WRRO
- Strategic planning of a joint SARS-CoV-2 and influenza vaccination campaign in the UK. Vaccines, 12(2). View this article in WRRO
- Placing a value on increased flexible vaccine manufacturing capacity for future pandemics. Vaccine, 41(14), 2317-2319. View this article in WRRO
- Vaccines on demand, part II: future reality. Expert Opinion on Drug Discovery, 18(2), 119-127.
- Techno-Economic Evaluation of Novel SARS-CoV-2 Vaccine Manufacturing in the Insect Cell Baculovirus Platform. International Journal of Technology, 13(8), 1630-1639.
- A blueprint for quality by digital design to support rapid RNA vaccine process development, manufacturing & supply. Vaccine Insights, 01(04), 219-233.
- GMMA as an alternative carrier for a glycoconjugate vaccine against Group A Streptococcus. Vaccines, 10(7). View this article in WRRO
- Optimization of lipid nanoparticles for saRNA expression and cellular activation using a design-of-experiment approach. Molecular Pharmaceutics, 19(6), 1892-1905. View this article in WRRO
- Quality by Design for enabling RNA platform production processes. Trends in Biotechnology, 40(10), 1213-1228. View this article in WRRO
- Comparative sustainability study of energy storage technologies using data envelopment analysis. Energy Storage Materials, 48, 412-438. View this article in WRRO
- Pandemic-response adenoviral vector and RNA vaccine manufacturing. npj Vaccines, 7(1). View this article in WRRO
- Stability modelling of mRNA vaccine quality based on temperature monitoring throughout the distribution chain. Pharmaceutics, 14(2). View this article in WRRO
- Model-based planning and delivery of mass vaccination campaigns against infectious disease: application to the COVID-19 pandemic in the UK. Vaccines, 9(12). View this article in WRRO
- Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases. npj Vaccines, 6(1). View this article in WRRO
- Correction: Resources, production scales and time required for producing RNA vaccines for the global pandemic demand (Vaccines, (2021), 9, 1, 10.3390/vaccines9010003). Vaccines, 9(3).
- Enhancing vaccine platforms : computational models accelerate development, manufacturing, and distribution. BioProcess International. View this article in WRRO
- Resources, production scales and time required for producing RNA vaccines for the global pandemic demand. Vaccines, 9(1). View this article in WRRO
- Rapid development and deployment of high‐volume vaccines for pandemic response. Journal of Advanced Manufacturing and Processing, 2(3). View this article in WRRO
- A model‐based quantification of the impact of new manufacturing technologies on developing country vaccine supply chain performance : a Kenyan case study. Journal of Advanced Manufacturing and Processing, 1(3). View this article in WRRO
- Emerging Technologies for Low‐Cost, Rapid Vaccine Manufacture. Biotechnology Journal, 14(7), 1-2.
- Emerging technologies for low‐cost, rapid vaccine manufacture. Biotechnology Journal, 14(1). View this article in WRRO
- Framework for WASH sector data improvements in data-poor environments, applied to Accra, Ghana. Water, 10(9). View this article in WRRO
- Electricity generation technologies: Comparison of materials use, energy return on investment, jobs creation and CO2 emissions reduction. Energy Policy, 120, 144-157. View this article in WRRO
- Preclinical testing of an oncolytic parvovirus in Ewing sarcoma : protoparvovirus H-1 induces apoptosis and lytic infection in vitro but fails to improve survival in vivo. Viruses, 10(6). View this article in WRRO
- Preclinical testing of an oncolytic parvovirus : standard protoparvovirus H-1PV efficiently induces osteosarcoma cell lysis in vitro. Viruses, 9(10). View this article in WRRO
- Development of a synthetic gene network to modulate gene expression by mechanical forces. Scientific Reports, 6(1). View this article in WRRO
- Comparison between direct and reverse electroporation of cells in situ: a simulation study.. Physiological Reports, 4(6). View this article in WRRO
- Mammalian synthetic biology: emerging medical applications. Journal of the Royal Society, Interface, 12(106). View this article in WRRO
- A novel high-throughput platform for siRNA transfection of primary mammalian cells. Atherosclerosis, 237(2), e14-e14.
- Systems and synthetic biology of the vessel wall.. FEBS Letters, 586(15), 2164-2170. View this article in WRRO
- Computational investigations on the electronic structure and reactivity of thiourea dioxide: sulfoxylate formation, tautomerism and dioxygen liberation. Journal of Sulfur Chemistry, 31(1), 27-39.
- ‘Super-reduced’ iron under physiologically-relevant conditions. Dalton Trans., 39(6), 1464-1466.
- The electronic structure of biologically relevant Fe(0) systems. International Journal of Quantum Chemistry, 110(10), 1848-1856.
- A new route to carbon monoxide adducts of heme proteins. Journal of Porphyrins and Phthalocyanines, 12(10), 1096-1099.
- Inflammatory- and immune responses in relation to bacterial replication in mice following re-infections with Chlamydophila pneumoniae. Inflammation Research, 57(6), 287-295.
- Expression of bacterial genes and induction of INF-γ in human myeloid dendritic cells during persistent infection withChlamydophila pneumoniae. FEMS Immunology & Medical Microbiology, 52(3), 324-334.
- Anion exchange HPLC monitoring of mRNA in vitro transcription reactions to support mRNA manufacturing process development. Frontiers in Molecular Biosciences, 11. View this article in WRRO
Book chapters
- Quality by design and techno-economic modelling of RNA vaccine production for pandemic-response, Computer Aided Chemical Engineering (pp. 2167-2172).
- Optimal design and planning of supply chains for viral vectors and RNA vaccines, Computer Aided Chemical Engineering (pp. 1633-1638).
- Computationally Designed Recombinant-DNA-Based Compounds Production Driven in Plants During Secondary Metabolism and Their Implication in Antimalarial Therapies, Natural Bio-active Compounds (pp. 127-146). Springer Singapore
- An In situ electroporation and flow device for mechanotransduction studies, Microarrays Principles Applications and Technologies (pp. 49-67).
Preprints
- Analysis of mRNA multimerisation (aggregation) using non-denaturing ion-pair reversed-phase HPLC, American Chemical Society (ACS).
- Multiple Gaussian process models based global sensitivity analysis and efficient optimization of in vitro mRNA transcription process, arXiv.
- Engineering an E. coli -based in vivo mRNA manufacturing platform, Wiley.
- Pandemic-response adenoviral vector and RNA vaccine manufacturing, openRxiv.
- In vitro transcription for RNA vaccines and therapeutics: a quality-by-design perspective on manufacturability. Biotechnology Advances, 93. View this article in WRRO
- Research group
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For the latest info on our research and team, please visit our research team website.
Our mRNA manufacturing process development lab received the Laboratory Efficiency Assessment Framework (LEAF) Silver Award.
- Grants
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Current grants
Date Funder Role Title Funding amount 1 July 2026 - 30 June 2029 Innovate UK, Contracts for Innovation; UK Official Development Assistance (ODA) via DHSC, UK Vaccine Network Project. Principal Investigator RNAboxTM: Automated and digitalised RNA process-in-a-box for rapid outbreak-response disease-agnostic RNA vaccine/therapeutic development and manufacturing at high-quality and low cost £5,658,780 1 Oct 2024 – 30 Sep 2027 Coalition for Epidemic Preparedness Innovations (CEPI) Principal Investigator RNAboxTM: An automated continuous closed RNA platform process-in-a-box for rapid outbreak-response disease-agnostic RNA vaccine development and mass-manufacturing at high-quality and low-cost £3.7 million
(US $4.8 million)1 Apr 2024 – 31 Mar 2027 Biotechnology and Biological Sciences Research Council (BBSRC)
BB/Y007514/1 · Engineering Biology, Mission AwardsCo‑Investigator Electrospun mucoadhesive matrices for polymersome-mediated mRNA vaccine delivery £2,382,846 1 Nov 2023 – 1 Nov 2028 UK Department of Health and Social Care & Engineering and Physical Sciences Research Council (EPSRC)
Hub, UK Vaccine NetworkCo‑Investigator UK-south-east Asia-vaccine manufacturing research hub £7.6 million 1 Oct 2023 – 30 Sep 2027 Engineering and Physical Sciences Research Council (EPSRC)
Doctoral Training Partnership with RedShift BioAnalyticsCo‑Investigator Quantification of double-stranded mRNA impurities using microfluidics modulation spectroscopy £130,000 1 Oct 2023 – 30 Sep 2027 Biotechnology and Biological Sciences Research Council (BBSRC)
iCASE PhD studentship with AstraZeneca PlcCo‑Investigator Synthetic Biology-Based Polymerase and Promoter Engineering for Production of Next-Generation RNA Therapeutics £84,000 Previous grants
Date Funder Role Title Funding amount Jul 2023 - Jul 2024 Biotechnology and Biological Sciences Research Council (BBSRC)
BB/X018989/1 · ALERT 2022Co‑Investigator NanoAnalyzer: An emerging technology to analyse life at the nanoscale £242,400 1 Oct 2023 – 31 Mar 2026 Innovate UK
SBRI: Vaccine development for potential epidemic diseases, UK Vaccine NetworkPrincipal Investigator Automated and digitalised RNA process-in-a-box for rapid outbreak-response disease-agnostic RNA vaccine/therapeutic development and manufacturing at high-quality and low cost £2 million 6 Dec 2021 – 30 Oct 2024 Wellcome Leap
RNA Readiness + Response (R3)Principal Investigator Digitalised, small-scale and high-throughput process for distributed and automated RNA production for therapy and pandemic preparedness Multi-million USD
(confidential)1 Jan 2022 – 31 Jul 2022 UK Research and Innovation (UKRI)
Research England: HEIF — Covid RecoveryCo‑Investigator Innovating the process of RNA vaccine and therapeutic manufacturing – building external partnerships and exploring commercialisation opportunities £74,331 20 Jul 2020 – 19 Jan 2022 UK Research and Innovation (UKRI)
EP/V01479X/1 · COVID-19Co‑Investigator Meeting the UK demand for COVID-19/SARS-CoV-2 vaccines via integrated manufacturing and supply chain optimisation £445,000 1 Sep 2020 – 31 Aug 2022 Wellcome Trust
220503/Z/20/Z · Innovator AwardsCo‑Investigator A pathway to a live-attenuated whole parasite malaria vaccine £727,458 1 Sep 2020 – 31 Aug 2021 Kidney Research UK
Ref. 2548 · Paediatric InnovationCo‑Investigator Cell catcher: developing a new method for cell isolation and preservation from urine samples of Bardet-Biedl Syndrome patients £39,997
- Teaching activities
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- I am a Fellow of the Higher Education Academy and I am passionate about teaching and training the next generation of chemical and biological engineers.
- I am supervising and co-supervising the PhD projects in the field of mRNA production, purification, formulation and analysis in our research team.
- I am teaching the following modules: 1) CMB325/CMB456 Biopharmaceutical and Vaccine Manufacturing, 3rd Year UG & M.Sc., Module Leader & Lecturer; 2) CMB135 Introduction to Bioengineering, 1st Year UG, Lecturer
- Professional activities and memberships
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- July 2019 – Present. American Institute of Chemical Engineers (AIChE).
- Nov 2018 – Present. Institution of Chemical Engineers, London (IChemE), U.K., Professional Member.
- June 2018 – Present. European Federation of Biotechnology (EFB).
- June 2018 – Present. European Biotechnology Network (EBN).
- June 2018 – Present. Developing Countries Vaccine Manufacturers Network (DCVMN).
- May 2018 – Present. The Network in Bioprocessing (BioProNET), a BBSRC Network in Industrial Biotechnology and Bioenergy co-sponsored by EPSRC (U.K. based).
- April 2018 – Present. Vaccine Research Network (VRN) at Imperial College London.
- February 2012 – Present. American Association for the Advancement of Science (AAAS).
I am regularly invited to speak at scientific and industry conferences, and to advise policy experts, non-governmental organisations and companies. I have advised industry and global health organisations on mRNA manufacturing, including as a member of the Sanofi mRNA CMC Advisory Board and the Pfizer mRNA Technology Advisory Board, and through techno-economic modelling consultancy for the WHO mRNA Technology Transfer Hub.