DNA and RNA are the building blocks of life. They contain the information the cell requires to synthesise protein and to replicate itself. These polymers are the repositories of genetic information. DNA looks like a twisting ladder, a double helix. RNA is typically only half a ladder. Both of these molecules are called nucleic acids. They are made up of four bases, adenine, guanine, cytosine, thymine or uracil. Now researchers have created six synthetic bases to further the dimensions of synthetic biology.

Synthetic biology is redesigning the building blocks of life. Its purpose is to serve the needs of humanity. It offers the power of designing and building cells with novel functions. Synthetic genomics, a field of synthetic biology, uses aspects of genetic modification on pre-existing life forms with the intent of producing some product or desired behaviour on the part of the life form so created. Synthetic genomics makes use of custom-designed base pairs. Synthetic genomics is extremely promising area of research, and its vision is to utilise genetic codes that are not composed of the four base pairs of DNA that are currently used by life.

In the year 2010 researchers from the J Craig Venter Institute in Maryland, US created a synthetic copy of a prokaryotic genome and used it to commandeer the cell of a closely related species. Using this approach it was possible to manipulate the genome on a significantly larger scale. It also paved way to completely redesign the genomes. The potential application of this landmark technology include developing innovative ways to produce energy, creating novel sensors to monitor the environment or building bacterial factories to churn out medicines. The next challenge in the researcher’s agenda was to build genetic circuits. So far, researchers have been able to design short (15,000-25,000 base-pairs long) genetic circuits. One of the limitations was combining those genes into a single network. Researchers were not yet sure, what is the better way — synthesise whole genomes or just synthesise the parts you want to change. Some synthetic biologists say that the technique might one day also allow researchers to remake extinct organisms, or catalogue species diversity simply by storing sequences. One of the important outcomes of the research is that it has given us the ability to construct long base pair chains cheaply and accurately on a large scale. In other words, it has shown us the possibility to work with genomes that do not exist in nature.

The field of synthetic genomics has entered a new era with the announcement by the researchers from Europe and the US that they have created six synthetic bases. These researchers started their work on the premise that many different polymers could serve the roles that of RNA and DNA in living organisms. The researchers created these bases by replacing the sugar groups on the existing bases, and then used DNA as a template to create xeno-nucleic acids (XNA). They called the synthetic bases ANA, FANA, LNA, TNA, CeNA and HNA. XNA’s ladders are made of different sugars. For example, if arabinose stands in for deoxyribose, you get ANA instead of DNA; if it is cyclohexane you get CeNA. These studies have revealed the profound influence of backbone, sugar, and base chemistry on nucleic acid properties and function. XNA’s are tougher than DNA and RNA. Acids and enzymes can break DNA/RNA easily, but XNA’s have no such problem. “Their unnatural nature makes them invulnerable to enzymes, extreme pH values, and other harsh conditions.” According to the researchers, these XNAs have the capacity for Darwinian evolution and folding into defined structures. What the researchers conveyed to us was that heredity and evolution are not limited to DNA and RNA, but are likely to be emergent properties of polymers capable of information storage. The work gave the researchers in the area of synthetic genomics a general strategy to replicate and evolve a broad range of synthetic genetic polymers. It is based on a chemical framework capable of specific base pairing with DNA, the engineering of polymerases that can synthesise XNA from a DNA template, and the engineering of polymerases that can reverse transcribe XNA back into DNA. The editorial where the research was published (Science, 2012, American Association of Advancement of Science) thus concludes about the path breaking research: “The work heralds the era of synthetic genetics, with implications for exobiology, biotechnology, and understanding of life itself. Construction of genetic systems based on alternative chemical platforms may ultimately lead to the synthesis of novel forms of life.” Every part of the ladder is up for alterations. This is just the beginning, say the researchers. Of course, the researchers are aware of the fact that they should not do something that can be done by using DNA or RNA. XNA’s are not replacement of DNA or RNA. An artificial can’t be the replacement of a natural one if that is available. zz

(The writer is a biotechnologist and ED, Birla Institute of Scientific Research, Jaipur)