Unnatural DNA

Scientists from The Scripps Research Institute (TSRI) have engineered a bacterium whose genetic material includes an added pair of man-made DNA ‘letters’ or bases apart from the existing pairs. The cells of this unique bacterium is capable of replicating the unnatural DNA bases more or less normally as long as it is supplied with molecular building blocks.

Living organisms on earth are encoded by only two pairs of DNA bases; A-T and C-G (adenine-thymine, cytosine-guanine). Researchers in the experiment created an organism which had these two DNA bases and added the third unnatural pair of bases in the bacterium to expand the boundaries of DNA biology and encode new proteins.

However, adding the pair had its own obstacles. Firstly the pair had to bind with an affinity similar to that of the natural pairs- A-D and C-G. The unnatural base would also have to line up along the existing pairs in a zipper-like stretch of DNA. It was also required of them to un-zip and re-zip smoothly when working on by natural polymerase enzymes during DNA replication and transcription into RNA. The second challenge was to protect the new DNA from being attacked and removed by the natural DNA repair mechanisms.

The man made DNA known as plasmid was then inserted in the cells of the common bacterium E.coli. It contained the natural base pairs along with two man-made molecules; d5SICS and dNAM. The pair was then added to a fluid solution outside the cell to supply them with molecular building blocks as they aren’t present naturally in the cells. The semi-synthetic plasmid replicated reasonable speed and accuracy without hampering the growth of E. Coli cells and showed no signs of losing its unnatural base pairs to DNA repair mechanisms.

The team led by Professor Flyod E. Romesberg achieved a major breakthrough when in 2008 they learned of nucleoside molecules that can hook up across a double strand of DNA in a similar way like that of natural one. This led to the thought that the unnatural DNA can replicate the natural one in the presence of right enzymes. Romesberg had been working since 1990 to find pairs of molecules that could act as new, functional DNA bases and create organisms that never existed before. They are of the opinion that this could even lead to tailor protein therapeutics and diagnostics to laboratory reagents to have desired functions.