The aim is to develop a simple, low cost means for the chemical synthesis of 50-500 gram quantities of oligonucleotides which can be utilized for antisense-DNA therapeutics and diagnostics. The research objectives are to investigate improved chemistries, to assemble a manual device which will utilize solid-phase cyanoethyl phosphoramidite or phosphonate chemistries and to test the system in the synthesis os 15-25 residue sequences. The research will involve the development of (a) a new solid support or a new means of handling large amounts of the existing solid supports and (b) a means to recycle the costly DNA synthons so that they can be used in large excess to maximize stepwise yields. The capability of high stepwise yields is routine in small scale, commercial instruments and is an important feature for larger scale synthesis in order to simplify the subsequent purification steps. The potential applications of the research are for the rapid and economical preparation of quantities of oligonucleotide that are necessary for clinical testing or for eventual manufacturing of therapeutic drugs or diagnostic reagents. These developments will be important achievements in terms of economic competitiveness. Improved methods for gram amounts of chemically synthesized DNA will accelerate drug development, reduce cost and enhance medical applications of biotechnology products.
