The Yomics approach takes advantage of the fact that a “draft” of the entire human genome sequence is available and, most important, that accurate annotations of the sequences of each human chromosome are being released. The knowledge of the sequence of virtually all human genes allow their physical isolation by using the well established technique of Polymerase Chain Reaction (PCR).
Oligonucleotides, annealing at the 5’ and 3’ ends of each genes, are designed and synthesized and all genes are amplified starting from a convenient source of human genes (cDNA preparations from mRNAs derived from different cells and tissues are most convenient). Once isolated, each gene can be expressed using recombinant DNA technologies and the corresponding recombinant protein can be purified. Finally, all human recombinant proteins thus isolated are used to immunize laboratory animals so as to obtain specific antibodies against each protein.
The overall strategy is straightforward, however, the technological challenges are remarkable. For the approach to be effective, several thousands of recombinant proteins and antibodies have to be produced in a reasonable timeframe. These ambitious goal can be reached only if efficient technologies amenable to high-throughput formats are in place. In particular, a solid bioinformatic platform must be available to select all genes, scan them and automatically design oligonucleotides for gene amplification. Once designed, the oligonucleotides have to be synthesized.
This implies the existence of a robust DNA synthesis facility with a output capacity of several thousands oligonucleotides per year. Also crucial to the success of the strategy are the cloning, expression and protein purification technologies available, which have to guarantee the production of large batteries of proteins per year. In particular, a large number of genes have to be simultaneously amplified, inserted into appropriate vectors and efficiently expressed in convenient expression systems.
Furthermore, for the production of polyclonal antibody against each purified recombinant protein, an efficient animal house with the capacity of housing and treating several thousands of animals simultaneously must be available.
Know-how, technologies and infrastructures necessary to carry out this experimental activity are all available at PRIMM Srl., one of the founders of Externautics. Indeed, several hundreds of recombinant proteins and antibodies are already available and ready to be used for target identification.