Abstract
DNA, the fundamental genetic polymer of all living organisms on Earth, can be chemically modified to embrace novel functions that do not exist in nature. The key chemical and structural parameters for genetic information storage, heredity, and evolution have been elucidated, and many xenobiotic nucleic acids (XNAs) with non-canonical structures are developed as alternative genetic materials in vitro. However, it is still particularly challenging to replace DNAs with XNAs in living cells. This review outlines some recent studies in which the storage and propagation of genetic information are achieved in vivo by expanding genetic systems with XNAs.
Highlights
Bacillus phages SPO1, SP8, H1, 2C, and SP82, thymidine is completely replaced by 5hmdU [10].DNA is the fundamental genetic material of all living organisms on Earth that stores and propagatesThymidine is substituted for deoxyuracil in the whole genome of Bacillus subtilis bacteriophages genetic information
A variety of unnatural nucleic acids have been synthesized by replacing natural bases, sugars, and phosphate linkages with artificial structures to investigate their potential as alternative genetic materials
Engineered polymerases promoted the application of xenobiotic-nucleic acids (XNAs) as alternative genetic materials in vitro
Summary
Bacillus phages SPO1, SP8, H1, 2C, and SP82, thymidine is completely replaced by 5hmdU [10]. Specific metabolic pathways are discovered in these phages that produce altered intracellular dNTP pools to synthesize modified DNA that are capable of escaping from host DNA repair systems, providing a possible method of using living cells with engineered genes that mimic phage genes for the incorporation of synthetic nucleotides into artificially built genetic systems [13,14]. To investigate the key chemical and structural parameters for genetic information storage, heredity, and evolution in vitro, a series of xenobiotic-nucleic acids (XNAs) are synthesized by replacing natural bases, sugars, and phosphate linkages with their unnatural counterpart. Some of these XNAs can mimic natural nucleic acids to form a stable double helix between DNA/RNA or themselves following Watson–Crick base-pairing rules. We hope that this review will encourage more systematic research on the exploration of XNA-based synthetic biology
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