http://www.i-sis.org.uk/Mass_Genome_Engineering.php
headline:
Mass Genome Engineering
Whole microbial genomes can be changed at will simultaneously and
rapidly; with large implications for safety Dr Mae-Wan Ho
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Whole genome engineering
One major way in which synthetic biology goes beyond conventional
genetic engineering is in the manipulation of entire genomes, both in
assembling it from pieces, as genome sequence data become available,
and in modifying genes scattered over entire genomes. It must be
emphasized that these techniques work as intended only in microbes
where recombination between homologous (similar) nucleic acid
sequences is the rule. In plants and animals, however, non-homologous
recombination between dissimilar sequences predominates, and it is
very difficult to target genes precisely. That is why genetic
modification of crops and livestock is inherently uncontrollable and
hazardous, as people like me have been stressing since it all began;
and we have been proved right (see [1] GM is Dangerous and Futile,
SiS 40). Synthetic biologists must proceed with caution in targeting
plant and animal genomes, because the unpredictability and potential
hazards are multiplied many times over.
The motivation for genome engineering, according to researchers Peter
Carr at Massachusetts Institute of Technology, and George Church at
Harvard Medical School, Cambridge, Massachusetts [2], is to understand
through building, to produce medicines and biofuels with a genome
optimized for the purpose, for example, to use microbes as biosensors,
for bioremediation, to hunt and destroy cancer cells; to instruct our
own cells to minimize the risk of septic shock; to produce organisms
with fundamentally altered codon usage, which could prevent an
engineered lab strain using acquired genes, and donating its
engineered features to wild organisms. Or simply, the motivation is
“build to creatively explore.”
Examples of genome engineering include Craig Venter Institute’s
construction of the first microbial genome from commercially available
cassettes [3]; the deletion of many large segments of E. coli genome
to get rid of unstable DNA elements; the transfer of much of one
Archean bacteria genome into eubacteria genome; decomposing the T7
bateriophage genome into many reconfigurable modules; making large
numbers of targeted changes to a genome simultaneously (see below);
and developing a purified translation system useful for in vitro
prototyping of genetic functions without requiring moving genes into
living cells. The manipulation of DNA segments >100 kbp in the first
three examples relied heavily on in vivo recombination techniques. ...
(cont)