EXTENDING THE CHEMISTRY THAT SUPPORTS GENETIC INFORMATION-TRANSFER IN-VIVO - PHOSPHOROTHIOATE DNA, PHOSPHOROTHIOATE RNA, 2'-O-METHYL RNA, AND METHYLPHOSPHONATE DNA

DNA and RNA are the polynucleotides known to carry genetic information in life, Chemical variants of DNA and RNA backbones have been used in structure-function and biosynthesis studies in vitro, and in antisens e pharmacology, where their properties of nuclease resistance and enha nced cellular uptake are important, This study addressed the question of whether the base(s) attached to artificial backbones encodes geneti c information that can be transferred irt vivo, Oligonucleotides conta ining chemical variants of DNA or RNA were used as primers for site-sp ecific mutagenesis of bacteriophage f1, Progeny phage were scored both genetically and physically for the inheritance of information origina lly encoded by bases attached to the nonstandard backbones, Four artif icial backbone chemistries were tested: phosphorothioate DNA, phosphor othioate RNA, 2'-O-methyl RNA and methylphosphonate DNA, All four were found capable of faithful information transfer from their attached ba ses when one or three artificial positions were flanked by normal DNA, Among oligonucleotides composed entirely of nonstandard backbones, on ly phosphorothioate DNA supported genetic information transfer in vivo .