Gene synthesis on microchips.

With gene synthesis we will in future be able to synthesize complete genomes. From there, we will be able to answer essential biological questions, for example, how chemical reactions proceed within a cell. The first step, genome sequencing, especially of the human genome, has created a huge amount of data. It is currently estimated that humans have about 25000 genes. Chemically speaking, genes are merely defined sequences of long DNA stretches. In the last 40 years, methods for the chemical synthesis of DNA have improved drastically. These processes are based on the stepwise coupling of individual nucleotide building blocks to yield oligonucleotides. These in turn, arrange themselves into double-stranded DNA owing to their base complementarity. Hydrogen bonding followed by chemical or chemoenzymatic ligation of the phosphoric esters results in the stable duplexes. By exploiting this principle, Khorana and co-workers were able to synthesize the first gene in 1970, the yeast tRNA gene. Since then, synthetic methods have been refined, most noteworthy by the application of the polymerase chain reaction (PCR), and the goals have becomemore ambitious. The subsequent years witnessed the syntheses of the following genes: a-interferon (1985), the interleukin-2 receptor a (1987), and a plasmid (1990). The year 2002 saw the synthesis of a polio virus DNA with around 7500 base pairs. Its biological activity was proven by its infectivity. The synthesis of the bacteriophage FX174 with 5386 base pairs was reported in 2003; this molecule was first sequenced by Fred Sanger with the newly developed dideoxy sequencing method. The longest recorded gene