Since the mapping of the human genome in 2003, synthetic biology has reached a new milestone. British researchers are now tackling the synthesis of human DNA (in other words, the creation of an artificial human genome), opening up unprecedented possibilities in medicine and biotechnology.
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Funded with £10 million by Wellcome, the SynHG project brings together scientists from the universities of Oxford, Cambridge and Manchester. The goal? To design purely synthetic chromosomes to better understand how our DNA works and develop innovative therapies.
The promises of a synthetic genome
Unlike gene editing (such as CRISPR), which is "limited" to making modifications to a genome, synthesis allows for the complete reconstruction of DNA sequences from scratch. This approach could lead to virus-resistant cells or safer organ transplants.
Recent advances with bacterial and yeast genomes show that the technique is viable. However, the human genome, which is far more complex, will require decades of research.
A synthetic chromosome, representing 2% of the genome, will be tested initially. The results could accelerate the fight against genetic diseases and aging.
A project with major ethical implications
Genome manipulation raises societal questions, particularly about the risks of eugenic misuse. To address these, the project includes a component led by Joy Zhang (University of Kent), studying the ethical and legal implications.
Public consultations will be conducted worldwide to regulate future applications. The aim is to prevent inequalities in access and malicious uses.
Despite these precautions, some scientists, like Bill Earnshaw (University of Edinburgh), fear a loss of control. The synthesis of human DNA could ultimately transform our relationship with life.
Going further: What are the risks of synthetic genomes?
The creation of artificial human DNA raises significant biosafety concerns. Unlike the targeted modifications allowed by CRISPR, the complete synthesis of genomes could, in theory, enable the design of custom pathogens or the resurrection of eradicated viruses. Strict protocols exist to verify synthesized sequences, but the risk of misuse by malicious or non-state actors worries biosecurity experts.
Ethically, this technology could exacerbate inequalities in access to medical advances. Therapies based on synthetic genomes, potentially expensive, risk being available only to certain populations, widening global health disparities. Moreover, the possibility of profoundly modifying the human genome revives fears of eugenics, particularly with the specter of "designer babies" with selected genetic traits.
Finally, scientific uncertainties remain. Even with a perfectly controlled DNA sequence, the interactions between synthetic genes and natural cellular mechanisms are still poorly understood. An artificial genome could cause unexpected effects, such as dangerous immune responses or epigenetic disruptions. These risks demand not only robust regulatory frameworks but also increased transparency in research and experimentation.
How does DNA synthesis work?
DNA synthesis relies on an automated chemical process that sequentially assembles nucleotides (A, T, C, G) according to a predefined sequence. Modern machines use the phosphoramidite synthesis method, where each layer of nucleotides is added step by step, with specific reagents to link the bases together. This process, although precise, is still limited to fragments of a few hundred base pairs, requiring enzymatic assembly techniques to form longer sequences.
For genomes like the human one, scientists combine molecular biology and bioinformatics. After synthesizing the fragments, they are assembled in model cells (such as yeast or bacteria), capable of "stitching" the DNA together using natural recombination mechanisms. Algorithms then verify the accuracy of the sequence, correcting potential errors introduced during synthesis or assembly.
Recent advances in robotics and artificial intelligence are significantly accelerating this process. Automated platforms can now produce thousands of DNA fragments in parallel, while AI optimizes sequences to avoid unstable or toxic regions for cells. Despite these advances, synthesizing an entire human chromosome remains a challenge due to its size and the complexity of its non-coding regions, whose exact role is still poorly understood.
Article author: Cédric DEPOND