Forget gene therapy. How about a whole new genome?
That's the feat achieved by scientists from the J. Craig Venter Institute in Rockville, Md, and reported in the June 29, 2007 issue of Science The researchers transplanted the entire genome of one bacterium into another.
In itself, the work amounts to little more than dressing a bacterium in its cousin's coat. But speaking at a press conference, senior author Craig Venter called the finding "a huge enabling step" for synthetic biology, the construction of artificial chromosomes from scratch.
The Venter Institute also is working on creating such artificial chromosomes, but Venter declined to specify how close, or not, the researchers are to success. The Institute and its predecessors have been working for more than a decade to determine a so-called 'minimal genome' that is necessary to sustain life, based on a mix of theoretical biology and study of yet another member of the mycoplasma family, M. genitalium, a bacterium with a genome of only roughly 500 genes.
Venter acknowledged that "synthetic genomics remains to be proven," since the paper demonstrates only that it is possible to transplant one natural chromosome into a different natural organism.
The central problem the Science paper addresses is "once you have an entire chromosome, how do you activate it?," Venter told reporters. "If you view a chromosome as software, you need a system to boot up that software... We wanted to make sure the DNA itself could boot up the cell."
The researchers took intact genomic DNA from a bacterium known as Mycoplasma mycoides and injected it into a close relative, Mycoplasma capricolum, making sure that all regulatory proteins had been stripped off and the DNA was free of DNA-associated proteins, or 'naked'. They found that in some of the transplanted cells, after a few days the donor genome was expressed, while the host DNA was not, creating cells that are phenotypically identical to the donor strain.
How the donor genome takes over is still something of a mystery, but there are several possibilities. These range from simple segregation, where the donor and host chromosomes segregate into different cells during cell division after the transplant, to a hostile takeover of the host cell via restriction enzymes of the donor genome.
Co-author John Glass recently took part in a symposium sponsored by the Oxnard, Calif.-based Kavli Foundation, where he was one of 17 signatories on the so-called Illulisat statement, which calls for research aimed at merging molecular biology and nanotechnology to create cyborg cells, which, they believe, could offer solutions to problems as diverse as climate change, energy, health and water resources.
Asked to elaborate how exactly synthetic organisms could contribute to solving such problems, Venter was short on specifics. But he said that an artificial chromosome, which the institute also is working to create, will prove superior to modifying existing organisms, naming energy as a specific example. "We think that designer fuels based on bacterial metabolism will give us quite a range of opportunities," though he also noted that "we are very much basing even the synthetic chromosomes right now on what we see from reading the genomes of these organisms, to make sure that it's truly feasible" to get a working program of gene expression from an artificial chromosome.
Venter also acknowledged that the phenomenon may prove "difficult to replicate" in other organisms, where restriction enzymes chop up foreign DNA as soon as it is recognized itself. "Our hunch is that we can make this work in other species," his co- author Clyde Hutchison elaborated. "But you could think of a lot of barriers."