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Wang Lab  /  Research  /  Synthetic chimera

Synthetic chimera

Greater capacity in DNA manipulation is needed beyond 100-kb scale. Despite being feasible in making 4-mb Syn61 genome, the limitation to DNA manipulation at 100-kb scale in a single step by REXER still means that engineering of whole bacterial genomes at true genome scale is expensive and time consuming. This not only limits its applications in bacterial genome engineering, but also poses a fundamental challenge of scaling up when being applied to higher organisms and especially mammalian genomes. Human genome is 3 × 109 bases for a diploid, and 6 × 109 for a haploid, roughly 103 times bigger than the Syn61 genome. If the cost and time for the synthesis of Syn61 genome are extrapolated linearly for a mammalian genome, such a synthetic mammalian genome will cost multi-billion USD and take several millenniums to complete. Even individual chromosomes will take centuries or at least decades to assemble. Such impracticality can only be avoided with greater DNA manipulation capacities at megabase, 10-megabase or higher scale, or in another word, "true genome-scale".

We aim to develop capacities to manipulate DNA at megabase scale in a single step. With this capacity, we aim to rearrange, assemble, combine, subtract, and create genomes across distinct species and even genesis truly at genomic scale.

Through this project we aim to achieve the ability to assemble and stably carry foreign DNA of multi-mb scale on bacterial genome. With the expanded capacity to manipulate genomes at multi-mb scale, we attempt to echo the question first raised in ancient Greek mythology: would it be possible to make a "chimeric" lifeform combining different biological traits across species, or even across genus segregations? Generation of such an organism would likely provide numerous valuable insights, allowing us to observe both the biochemical and the phenotypical impacts of a synthetic genome "chimera" on the functions and forms of the artificially constructed hybrid lifeform.