Synthetic Genomics

Recent advancements in genomics, along with established knowledge about sequence variation, have set the stage for manipulation of genome sequences in the laboratory. The potential benefits of such genome re-engineering and assembly are huge. These benefits include uncovering the functions of genomic elements and reconstructing specific regions of the genome to improve organismal fitness. The fields that can benefit include crop improvement, industrial enzymes, vaccines, energy production and husbandry. Genome re-engineering also has far-reaching implications for human health and the fight against disease.

PharmaSeq has initiated a synthetic genomics program that provides improved methods and instrumentation for manufacturing large numbers of synthetic DNAs (oligonucleotides). These oligonucleotides are used to assemble large libraries of double-stranded (ds) DNA fragments that span long stretches of chromosomes. Such fragments can then be used to reconstruct genomes with any desired sequence. Large numbers of synthetic oligonucleotides (“oligo pools”) can also be used in research and diagnostic applications, including targeted DNA sequencing and multiplex DNA assays. PharmaSeq projects that the cost per nucleotide using its approach will be much less than that of current methods.

The purpose of the currently ongoing project is to develop and validate an improved method for synthesizing DNA de novo from nucleosides. The method, which is called “sequence-directed DNA synthesis”, involves the use of small electronic “p-Chips”, each of which transmits a unique ID number via RF when illuminated with laser light. DNA molecules are sequentially synthesized on p-Chips as solid phase. p-Chips provide the ability to associate a specific DNA sequence with the ID of the p-Chip as elongation occurs. A key part of the system is the sorter, which is a high-speed device that reads the ID of each p-Chip and then sorts the p-Chip into the appropriate reaction vessel based on the existing sequence and the base that is to be added next.

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