STIMULATION OF IN-VITRO PROLIFERATION OF MURINE LYMPHOCYTES BY SYNTHETIC OLIGODEOXYNUCLEOTIDES

To elucidate the properties of mitogenic nucleic acids, the ability of oligodeoxynucleotides to stimulate the in vitro proliferation of muri ne lymphocytes was investigated. The compounds tested were a series of oligodeoxynucleotides, synthesized with either phosphodiester or phos phorothioate chemistry and containing (dG) and (dC) alone or together. Among oligodeoxynucleotides tested, phosphorothioates were more activ e than phosphodiesters and stimulated thymidine incorporation under th e same conditions as mitogenic non-mammalian DNA. Mitogenesis was unaf fected by depletion of T cells, suggesting B cells as the predominant cell type stimulated. These results indicate that mitogenic nucleic ac ids need not have an extended polymeric structure and raise the possib ility that antisense compounds have immunologic activity, at least in animal models.