Directed Multiplex DNA Sequencing by Hybridization

41186 BIOS Laboratories, Inc. The ultimate goal of the Human Genome program is to obtain the entire sequence of the genetic makeup of the human body. This research has mostly encompassed large scale DNA sequencing projects, with interdisciplinary teams of biochemists, engineers, and computer specialists, which are beyond the resources of small to mid-sized laboratories. This project will develop an alternate, lower cost technique for directed DNA sequencing, utilizing hybridizations of Peptide Nucleic Acid (PNA) oligomer probes. PNA oligomers hybridize more stably and specifically to DNA targets than conventional oligonucleotides. Phase I is concerned with improvements in the three multiply repeated steps in the directed sequencing process: (1) probe assembly, (2) sequencing reactions and (3) gel electrophoresis. The technique allows the efficiency of directed sequencing, while avoiding most of the bottlenecks identified for the process. Commercial Applications and Other Benefits as described by the awardee: The development of modular PNA probes from pre-synthesized libraries should substantially reduce the cost of PNAs and extend further the applications of these novel molecules to DNA sequencing. The resources to be developed include PNA oligomer libraries, anchor primer kits for multiplex sequencing, and customized services.