Upshot of a series of four papers published over the last years (Gibson et al, 2010, Lartigue et al, 2009, Gibson et al, 2008, Lartigue et al, 2007), J. Craig Venter’s team now reports the successful transplantation of a chemically synthesized genome into a host bacterial cell (Gibson et al, 2010). As proof of principle, a slightly altered Mycoplasma mycoides genome (JCVI-syn1.0) was synthesized, assembled and transplanted into M. capricolum recipient cells.
This achievement results from the integration of several techniques developed in previous works: 1) a hierarchical strategy to assemble, via homologous recombination in yeast, a full genome from chemically synthesized overlapping fragments (Gibson et al, 2008); 2) a method to transform a full genome into a host cell and replace the recipient genome by the donor genome (‘transplantation’, Lartigue et al 2007); 3) a method to transplant DNA engineered in yeast into bacteria without being inactivated by the host restriction system (Lartigue et al, 2009). Finally, in the last work, systematic debugging methods were needed to identify a single base pair deletion that prevented productive transplantation (Gibson et al 2010).
The experiment represents certainly a highly symbolic milestone. A fascinating potential of this technology, if generalized and automated, is to enable the introduction of many genomic alterations simultaneously and, thus, to be able to reprogram cellular phenotypes with non-trivial genetic combinations that would have been impossible to identify with a sequential gene by gene approach. In this sense, while technically and ‘philosophically’ distinct, Venter’s approach appears complementary to multiplexed mutagenesis technologies that introduce simultaneously multiple modifications in a target genome (Wang et al, 2009).