In the May 20th issue of Science Express, a group led by Daniel Gibson, Hamilton Smith and J. Craig Venter published an article that got the full attention of scientists, bioethicists and IP attorneys worldwide: “Creation of a Bacterial Cell Controlled by a Chemically-Synthesized Gene. “ The methodology employed was well summarized by Elizabeth Pennisi in her introduction to the paper: “Synthetic Genome Brings New Life to Bacterium” (Science, 328, 958 (May 21, 2010)) and in the article itself, as well as by patentdocs.org, and so does not need undue replication here.
After the Venter group was able to successfully transfer the entire genome (one chromosome, in this case) of a simple bacterium to another related species, and demonstrated that they could synthesize an artificial chromosome that was labeled so it could be tracked, the group set about to synthesize the 1-million-base genome of the bacterium M. mycoides and transfer it into the related species M. capricolum. The starting-point sequence was available online (no patent problems there, Judge Sweet), so the group bought one thousand 1080-base sequences from a DNA-on-demand company and set about to assemble them into “a completely assembled synthetic genome.” (Note to file: How did the group select the individual 1080 base sequences they ordered? See US 2010/0041035 A1.)
A functional yeast clone was obtained and transplanted into M. capricolum. The synthetic genome was “watermarked” with preselected unique sequences so the group could tell it was “theirs”. Using a conventional marker gene allowed them to identify functional transformed bacteria that contained the synthetic chromosome, which they further characterized by sequencing and protein profiling. (Note to file: Use Fig. 1 of the Science paper to train junior biotech associates in modern transgenic methodologies.)
Although Ms. Pennisi states that commentators “emphasize that this work didn’t create a truly synthetic life form, because the genome was put into an existing cell,” Venter et al. are not quite so restrained. To quote from the Science paper:
“We refer to such a cell controlled by a genome assembled from chemically synthesized pieces of DNA as a ‘synthetic cell’ even though the cytoplasm of the recipient cell is not synthetic [Note to file; neither is the cell wall]. Phenotypic effects of the recipient cytoplasm are diluted with protein turnover and as cells carrying only the transplanted genome replicate. Following transplantation [of the synthetic genome] and replication on a plate to form a colony…progeny will not contain any protein molecules that were present in the original recipient cell….The properties of the [progeny] cells controlled by the synthetic genome are expected to be the same as if the whole cell had been produced synthetically (the DNA software builds its own hardware). “
A quick search for published patent applications directed to this feat (and its future) yielded Venter et al., published application US 2007/0264688 A1 (Nov. 15, 2007). Here are a few representative claims:
1. A method for constructing a synthetic genome comprising:
assembling nucleic acid cassettes that comprise portions of the synthetic genome, where at least one of the nucleic acid
cassettes is constructed from nucleic acid components that have been chemically synthesized, or from copies of chemically-
synthesized nucleic acid components.
2. The method of claim 1, wherein the genome is a non-naturally occurring genome.
14. The method of claim 1, wherein an entire synthetic genome is constructed from nucleic acid components that have been chemically synthesized,
or from copies of the chemically synthesized nucleic acid components.
32. A synthetic genome.
34. A synthetic cell comprising a synthetic genome.
38. A method comprising:
designing a synthetic genome;
constructing the synthetic genome;
introducing the synthetic genome into a biological system; and
expressing said genome.
How’s that for a glimpse into the future of “patenting life”?