Toward safe genetically modified organisms through the chemical diversification of nucleic acids.
It is argued that genetic proliferation should be rationally extended so as to enable the propagation in vivo of additional types of nucleic acids (XNA for 'xeno-nucleic acids'), whose chemical backbone motifs would differ from deoxyribose and ribose, and whose polymerization would not interfere with DNA and RNA biosynthesis. Because XNA building blocks do not occur in nature, they would have to be synthesized and supplied to cells which would be equipped with an appropriate enzymatic machinery for polymerizing them. The invasion of plants and animals with XNA replicons can be envisioned in the long run, but it is in microorganisms, and more specifically in bacteria, that the feasibility of such chemical systems and the establishment of genetic enclaves separated from DNA and RNA is more likely to take place. The introduction of expanded coding through additional or alternative pairing will be facilitated by the propagation of replicons based on alternative backbone motifs and leaving groups, as enabled by XNA polymerases purposefully evolved to this end.
Herdewijn
Piet
P
Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven.
Marlière
Philippe
P
D004247:DNA / Q000737:chemistry; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D030781:Organisms, Genetically Modified / Q000235:genetics*; D012313:RNA / Q000737:chemistry
D009696:Nucleic Acids; D012313:RNA; D004247:DNA; D012321:DNA-Directed RNA Polymerases; D004259:DNA-Directed DNA Polymerase