Scientists create tools to make life from scratch

Researchers in the USA have produced a complete synthetic genome in a development that could revolutionise the production of biotechnological products, including pharmaceuticals.

The scientists, based at the Institute for Biological Energy Alternatives in Maryland, have demonstrated that it is possible to assemble all the genetic components that make-up the genome of a simple living organism using readily-available resources.

This suggests that it may be possible to create new life forms from scratch that can fulfil a specific function, such as produce a protein-based drug, mop up pollutants in the environment or produce biofuels such as methane or hydrogen.

The IBEA researchers created a bacteriophage - a simple virus-like organism that infects bacteria - from short, single strands of synthetically produced, commercially available DNA. They used a process known as polymerase cycle assembly (PCA), an adaptation of the polymerase chain reaction (PCR), a widely-used technique for amplifying the amount of DNA in a sample, to assemble the genome.

Last year, researchers at Stonybrook University in New York, US, reported the first synthesis of a complete genome - in this case of poliovirus - which was found to be active by when it caused paralysis after being injected into mice.

The bacteriophage selected for the work, phiX714 (phi X), was the first organism to have its DNA completely sequenced and has been well-studied in the laboratory. Synthesis of its genetic code arrangement, which includes genes that overlap each other, requires very high accuracy making it easy to verify whether exact synthesis has occurred.

While not yet at the stage where a truly living organism has been created (viruses are not considered to be truly alive, lacking certain functions that a cell-based life form possesses), the assembly of the genome at least shows that the PCA approach is feasible, according to the IBEA researchers.

However, they caution a great deal more work must be done before a cellular genome, i.e. one of sufficient size to carry the number of genes required to support life, can be created.

The bacteriophage assembled in the present study consisted of around 5,386 base pairs, while the synthetic poliovirus contained around 7,500. This would represent a tiny proportion of the total number of base pairs needed to create a fully-functional genome capable of coding for all the elements needed to support life.

A fully-functional bacterial genome may include several million base pairs and code for a few thousand genes. At present, the estimate is that a synthetic genome might require as few as 300 genes to code for a viable organism, but many more genes - perhaps 1,000 - may be needed to add in the functionality needed to make a protein or metabolise a pollutant.

The IBEA researchers' aim is in time to insert a synthetic genome into a carrier cell which has had its existing DNA stripped out. But whether this will be enough to 'boot up' the genetic material and start life remains a fundamental unanswered question.

Leaving aside the technical obstacles that must be overcome, the IBEA team has high hopes for the synthetic genome technology. Potential applications include better, faster gene synthesis, in which any biotech agent that isderived from or uses a gene product - provided it is relatively small (10kb or less) - could be manufactured using the PCA technique.

Other applications could include faster, more accurate DNA-based vaccine production and improved phage therapy, for example, for treating antibiotic resistant infections, they note.

Craig Venter, a leading genome researcher who was instrumental in setting up the IBEA, believes that a near-term benefit of the technology could be the construction of so-called "cassette-based" organisms .

"Eventually we will be able to produce "cassettes" of particular genes or pathways that could be inserted into host organisms to conduct many types of functions",​ he noted.

For example, organisms could be engineered to improve production in a more environmentally sound way of pharmaceutical, textiles and plastics, replacing the use of petrochemicals, he noted.