In a landmark advancement for synthetic biology and genomic science, a team of Chinese researchers has successfully assembled large-scale synthetic human DNA and achieved its delivery into mouse embryos, marking a world-first in cross-species DNA transfer at such complexity. This milestone not only refines the technological frontier of human genome synthesis but also holds enormous potential for addressing currently untreatable genetic disorders.
The breakthrough, spearheaded by the State Key Laboratory of Synthetic Biology at Tianjin University, was recently detailed in the prestigious international journal Nature Methods under the title, “De novo Assembly and Delivery of Synthetic Megabase-Scale Human DNA into Mouse Early Embryos.”
The research was led by Yuan Yingjin, a prominent academician of the Chinese Academy of Sciences, and represents a key moment in efforts to understand how synthetic DNA can function within foreign biological environments.
At the heart of the project lies a novel method developed by the team known as SynNICE, which combines high-precision DNA assembly with cross-species chromosomal delivery. The technique begins with constructing large stretches of human genomic DNA in yeast cells. These yeast-hosted synthetic chromosomes are then extracted through a sophisticated technique called NICE (Nucleus Isolation for Chromosomes Extraction), which isolates the yeast nuclei intact, preserving the synthetic DNA.
The isolated nuclei containing the synthetic human chromosomes were then microinjected into early-stage mouse embryos. Remarkably, the embryos not only accepted the foreign human genetic material but also began transcribing it—demonstrating, for the first time, that synthetic human genes can be expressed inside a mouse cellular environment.
The research focused on the AZFa region of the human Y chromosome, a megabase-scale genetic segment known for its role in male fertility. Deletions or mutations in this area are linked to severe forms of infertility in men, with no effective clinical treatments currently available. The AZFa region is notoriously difficult to replicate due to its repetitive sequences and structural complexity, making the team’s successful synthesis and transfer all the more impressive.
What sets this study apart from earlier efforts in synthetic biology is the scale and fidelity of the transferred DNA, as well as the observation of active transcription—the critical first step toward gene expression and function—within a different species. This implies that not only can synthetic DNA be accurately built and moved between species, but it may also integrate into the host’s biological processes.
Experts believe this technology could have sweeping implications. In the near term, it opens the door to advanced modeling of genetic diseases, particularly those involving large chromosomal abnormalities. In the long term, it may pave the way for gene therapy breakthroughs, regenerative medicine, and even synthetic organ development, by allowing researchers to simulate or correct human genes in animals before moving toward clinical trials in humans.
Beyond reproductive medicine, this research feeds into a broader scientific ambition: constructing fully synthetic human chromosomes that could one day lead to the production of designer genetic modules for curing diseases, optimizing human health, or exploring human evolution.
The SynNICE method also offers a new platform for testing how synthetic DNA behaves in living organisms—enabling scientists to explore the interplay between artificial and natural genomes, understand regulatory networks, and evaluate the stability of synthetic chromosomes in real time.
According to Yuan Yingjin and his team, the next stages of research will likely involve testing other human genomic regions in similar cross-species models, refining the stability and expression efficiency of the transferred DNA, and exploring potential applications in reproductive biology and precision medicine.
This accomplishment places China at the forefront of global efforts in synthetic genomics and bioengineering, joining a small circle of countries capable of conducting megabase-scale human DNA assembly and transfer. It also highlights the potential for further innovation in genome editing technologies such as CRISPR, synthetic embryos, and custom gene circuits.
As synthetic biology continues to evolve rapidly, achievements like these signal a future where human-designed DNA could become a standard tool in treating disease, creating biological interfaces, and reshaping our understanding of life itself.
