DNA HYBRIDIZATION REACTIONS, DISCOVERED AND EXPLORED IN THE EARLY 1960S AND 70S, EXHIBIT NEARLY ABSOLUTE SPECIFICITY.

DNA HYBRIDIZATION REACTIONS, DISCOVERED AND EXPLORED IN THE EARLY 1960S AND 70S, EXHIBIT NEARLY ABSOLUTE SPECIFICITY. RESEARCHERS RECOGNIZED THAT THIS SPECIFICITY MIGHT MAKE IT POSSIBLE TO DEVELOP DNA-BASED DIAGNOSTIC AND THERAPEUTIC AGENTS. IN 1977, RESEARCHERS DISCOVERED HYBRID-ARREST OF TRANSLATION. ANTISENSE OLIGONUCLEOTIDES, RNAS, AND CDNAS HAVE NOW BEEN SHOWN TO HYBRIDIZE TO AND INHIBIT THE TRANS- LATION OF SPECIFIC MRNAS BOTH IN VITRO AND IN VIVO. SUCH SPECIFIC TRANSLATION INHIBITING COMPOUNDS ARE USEFUL IN STUDYING THE FUNCTION OF PARTICULAR MRNAS IN THE LIVING CELLAND COULD POTENTIALLY BE USED TO SELECTIVELY BLOCK THE GROWTH OF VIRUSES AND BACTERIA. THE MAJOR DIFFICULTY IS THAT THEY ARE LARGE POLYANIONS THAT ARE POORLY TAKEN UP BY CELLS AND ARE SUBJECT TO RAPID DEGRADATION BY NUCLEASES. SYNTHETIC OLIGONUCLEOTIDE PHOSPHOTRIESTERS (PTES) AND METHYLPHOSPHONATES ARE NON-IONIC, LIPOPHILIC MOLECULES THAT ARE STABLE TO NUCLEASES AND WELL TAKEN UP BY LIVING CELLS. DNA PHOSPHOTRIESTERS HYBRIDIZE TO BOTH RNA AND DNA IN VITRO AND CAN SELECTIVELY INHIBIT IN VITRO TRANSLATION. THUS DEFINED SEQUENCE PTES WOULD BE USEFUL IN THE STUDY OF MRNA FUNCTION AND PROCESSING IN VIVO. IN ADDITION, THESE AGENTS COULD, IF PROVEN SAFE AND EFFECTIVE, BE USED AS SPECIFIC ANDDESIGNABLE ANTIVIRAL AND ANTIBIOTIC AGENTS.