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Seidel, Z. P.; Assad-Garcia, N.; Paralanov, V.; Wu, F.; Chao, O.; Strychalski, E. A.; Romantseva, E. F.; Goshia, T.; Venter, J. C.; Glass et al.
We present a living, synthetic bacterial cell made by transplanting a complete genome into a dead cell. After killing Mycoplasma capricolum cells by chemically crosslinking their genome with Mitomycin C (MMC), we installed synthetic Mycoplasma mycoides genomes into the resulting dead cells using Whole Genome Transplantation (WGT)1,2. During WGT, a synthetic donor genome is placed into a recipient cell, thereby reprogramming that cell to adopt a new genetic identity3. WGT has only been demonstrated using species within one phylogenetic clade of Mollicutes bacteria4. A major barrier to expanding WGT to diverse bacterial species has been the inability to inactivate the recipient genome, leading to false positive transplants due to homologous recombination of antibiotic resistance markers from the donor genome into the recipient cell genome. Here, we address this key limitation by removing reliance on an antibiotic resistance marker to select for transplants; recipient cells are dead unless revived by the installation of a new genome. Our work demonstrates a general approach to fully inactivate the recipient cell genome, reports the first living synthetic bacterial cell constructed from non-living parts, and advances WGT for building engineered or synthetic cells for diverse applications.
In a zombie-synth-bio heist straight out of a mad-scientist flick, the Venter crew chemically “kills” Mycoplasma cells with Mitomycin C crosslinks, then stuffs their empty shells with synthetic genomes via whole-genome transplantation—reviving them as fully functional synthetic bacteria with zero selection-marker drama, like the ultimate microbial resurrection hack.
Shared by Osaka University Professor Wataru Aoki (@mighty_tora) hailing it as a “huge milestone” toward synthesizing life from non-life, with Japanese follow-ups explaining the dead-cell transplant trick that lit up the synth-bio world
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