New project to pioneer the principles of human genome synthesis

An ambitious new research project, SynHG (Synthetic Human Genome), is aiming to develop the foundational and scalable tools, technology and methods needed to synthesise human genomes. Through programmable synthesis of genetic material we will unlock a deeper understanding of life, leading to profound impacts on biotechnology, potentially accelerating the development of safe, targeted, cell-based therapies, and opening entire new fields of research in human health. Achieving reliable genome design and synthesis – i.e. engineering cells to have specific functions – will be a major milestone in modern biology.

The five-year multi-centre research project – supported by £10mn funding from Wellcome – involves researchers from the Universities of Cambridge, Kent, Manchester, Oxford, and Imperial College London. SynHG is led by Professor Jason Chin of the MRC Laboratory of Molecular Biology; he was also recently announced as the founding Director of the Generative Biology Institute at the Ellison Institute of Technology, Oxford, and a Professor at the University of Oxford.

A dedicated social science programme, led by Professor Joy Zhang of the Centre for Global Science and Epistemic Justice at the University of Kent, runs throughout the project alongside the scientific development. The programme will work with civil society partners around the world to actively explore, assess and respond to the socio-ethical implications of tools and technologies developed by SynHG.

The benefits of human genome synthesis to research and beyond

Since the completion of the Human Genome Project at the start of the century, researchers have sought the ability to write our genome from scratch. Unlike genome editing, genome synthesis allows for changes at a greater scale and density, with more accuracy and efficiency, and will lead to the determination of causal relationships between the organisation of the human genome and how our body functions. Synthetic genomes have the potential to open up brand new areas of research in creating targeted cell-based therapies, virus-resistant tissue transplantation and extensions may even enable the engineering of plant species with new properties, including the ability to withstand harsh climate.

To date, scientists have successfully developed synthetic genomes for microbes such as E. coli. The field of synthetic genomics has accelerated in recent times, and advances in machine learning, data science and AI showing promise, with synthesised DNA becoming more widely available. However, today’s technology is not able to produce large, more complex sections of genetic material, such as found in crops, animals and humans.

The research team are focusing on developing the tools and technology to synthesise large genomes exemplified by the human genome. Focusing on the human genome, as opposed to other model organisms such as mice, will allow researchers to more quickly make transformative discoveries in human biology and health.

Professor Jason Chin, Founding Director of the Generative Biology Institute at EIT, Oxford, said:

“The ability to synthesize large genomes, including genomes for human cells, may transform our understanding of genome biology and profoundly alter the horizons of biotechnology and medicine. With SynHG we are building the tools to make large genome synthesis a reality, and at the same time we are pro-actively engaging in the social, ethical, economic and policy questions that may arise as the tools and technologies advance. We hope that Wellcome’s support for this combination of approaches will help facilitate substantive societal benefit.”

A bold, ambitious project facing complex scientific challenges

SynHG focuses on developing the foundational tools and methods required to equip more researchers in the future. This research journey will potentially catalyse new technologies in the field of engineering biology, generating exciting discoveries about how cells use their genomes even before achieving complete genome synthesis.

The team of researchers hope to provide proof of concept for large genome synthesis by creating a fully synthetic human chromosome, which makes up approximately 2% of our total DNA. Initially, the team hope to establish methods where small changes are made to the sequence of a chromosome with minimal onward effect on the proteins that it produces.

Setting the foundation – testing the concept, iterating the methods, and embedding ethical considerations – could alone take many years. Even as engineering biology technologies improve, reliably building a complete synthetic human genome and meaningfully applying it to human health will likely take decades.

Michael Dunn, Director of Discovery Research at Wellcome, said:

“Our DNA determines who we are and how our bodies work and with recent technological advances, the SynHG project is at the forefront of one of the most exciting areas of scientific research. Through creating the necessary tools and methods to synthesise a human genome we will answer questions about our health and disease that we cannot even anticipate yet, in turn transforming our understanding of life and wellbeing.”

Embedding global socio-ethical discussions in scientific advancements

To effectively translate scientific ambition into meaningful and potentially profound societal benefits, it is essential that there is proactive and sustained engagement with the evolving socio-ethical priorities and concerns of diverse communities.

Wellcome is also funding Care-full Synthesis, a dedicated social research initiative conducting empirical studies with diverse publics worldwide. Led by Professor Joy Y. Zhang and hosted by the Centre for Global Science and Epistemic Justice (GSEJ) at the University of Kent, the project builds on GSEJ’s global network of academic, civil society, industry and policy partners to promote a new approach of science–society dialogue that is Open, Deliberative, Enabling, Sensible & Sensitive, and Innovative (‘ODESSI’).

Professor Joy Zhang, Founding Director of the GSEJ at the University of Kent said:

“With Care-full Synthesis, through empirical studies across Europe, Asia-Pacific, Africa, and the Americas, we aim to establish a new paradigm for accountable scientific and innovative practices in the global age—one that explores the full potential of synthesising technical possibilities and diverse socio-ethical perspectives with care.”

Over the next five years, the team will undertake a transdisciplinary and transcultural investigation into the socio-ethical, economic, and policy implications of synthesising human genomes. The project places particular emphasis on fostering inclusivity within and across nation-states, while engaging emerging public–private partnerships and new interest groups.

Through the generation of rich empirical data, the team will develop a toolkit to enable effective integration of careful thinking into the management, communication, and delivery of human genome synthesis. This work aims to substantially expand the practice of accountable science and innovation, reflecting the complex realities of a hyperconnected yet ideologically fragmented world. Care-full Synthesis will achieve this by advancing a fresh approach to engaging with global communities, ensuring that fast-moving science is accompanied by robust social and legal deliberation, and identifying innovative strategies to co-ordinate regional and global governance accounting for diverse social priorities and scientific pathways.

Additional quotes: 

Dr. Julian Sale, Group Leader in the Division of Protein & Nucleic Acid Chemistry at the MRC Laboratory of Molecular Biology, Cambridge said: "The ability to synthesise large segments of human chromosomes — or even entire genomes — will enable us to test current theories about how genes and other genetic elements interact to govern genome function with unprecedented precision and scale. The insights gained from this research will pave the way for designing and building safe and effective cell-based therapies with the potential to revolutionise biotechnology and medicine."

Professor Patrick Yizhi Cai, Chair of Synthetic Genomics at the University of Manchester said: "We are leveraging cutting-edge generative AI and advanced robotic assembly technologies to revolutionize synthetic mammalian chromosome engineering. Our innovative approach aims to develop transformative solutions for the pressing societal challenges of our time, creating a more sustainable and healthier future for all."

Professor Tom Ellis, Centre for Engineering Biology Institute at Imperial College London said: “Synthesis of chromosomes for bacteria and yeast has given us a new understanding of DNA and unlocks new approaches to biotechnology. Taking this to the next scale with the much larger chromosomes of mammalian cells is a challenge that will drive innovation.”

Notes to Editors:

The Wellcome-funded project is led by Professor Jason Chin* (Generative Biology Institute at Ellison Institute of Technology, Oxford / University of Oxford; MRC Laboratory of Molecular Biology) in collaboration with:

· Professor Patrick Cai* (University of Manchester)

· Professor Tom Ellis* (Imperial College London)

· Dr Julian Sale* (MRC Laboratory of Molecular Biology)

· Professor Joy Zhang (University of Kent)

*Also Associate Faculty at the Wellcome Sanger Institute, which is supporting the scientific project.