Synthetic polymers and their potential as genetic materials

  title={Synthetic polymers and their potential as genetic materials},
  author={Vitor B. Pinheiro and David Loakes and Philipp Holliger},
DNA and RNA are the only known natural genetic materials. Systematic modification of each of their chemical building blocks (nucleobase, sugar, and phosphate) has enabled the study of the key properties that make those nucleic acids genetic materials. All three moieties contribute to replication and, significantly, all three moieties can be replaced by synthetic analogs without loss of function. Synthetic nucleic acid polymers capable of storing and propagating information not only expand the… 
Mimicking DNA Functions with Abiotic, Sequence-Defined Polymers
This review highlights abiotic, sequence-defined polymers in their capacity to mimic the primary functions of DNA – data storage and retrieval, sequence specific self-assembly of duplexes, and replication and synthetic templating of new macromolecules.
A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids
Synthetic genetic polymers with an uncharged alkyl phosphonate backbone chemistry have been shown to enable genetic information transfer and evolution and provide a foundational methodology for their exploration as a source of novel functional molecules.
Transliteration of synthetic genetic enzymes
It is shown that an in vitro selected 2′-fluoroarabino nucleic acid (FANA) enzyme retains catalytic activity when its sequence is prepared as α-l-threofuranosyl nucleic acids (TNA), and vice versa, a TNA enzyme that remains functional when its sequences are prepared as FANA, providing new insight into the sequence-structure-function paradigm governing biopolymer folding.
Nucleic acids: function and potential for abiogenesis
The functional potential of RNA (and other nucleic acids) is examined with respect to self-replication, catalysis and assembly into simple protocellular entities.
Synthesis and polymerase recognition of a pyrrolocytidine TNA triphosphate
The synthesis and polymerase activity of a cytidine TNA triphosphate analog (6‐phenyl‐pyrrolocytosine, tCpTP) that maintains Watson‐Crick base pairing with guanine is described, expanding the toolkit of TNA building blocks available for in vitro selection.
A biologically stable DNAzyme that efficiently silences gene expression in cells
A xeno-nucleic-acid-modified version of the classic DNAzyme 10–23 is reported that achieves multiple-turnover activity under cellular conditions and resists nuclease digestion, and may provide a new route for nucleic acid enzymes to reach the clinic.
Nucleobases on the Primitive Earth: Their Sources and Stabilities
Nucleobases are nitrogen heterocycles that are key structural components of biological nucleic acids. Some theories for the origins of life suggest a role for environmentally supplied organic
Transcription of 4'-thioDNA templates to natural RNA in vitro and in mammalian cells.
The modifications of DNA with 2'-deoxy-4'-thionucleosides, so-called 4'-thioDNA, were found to act as templates for transcription with RNA polymerases both in vitro and in mammalian cells.
RNA modularity for synthetic biology
A better understanding and integration of three-dimensional RNA modularity at structural and functional levels is critical to the development of more complex, functional bio-systems and molecular machines for synthetic biology applications.


The XNA world: progress towards replication and evolution of synthetic genetic polymers.
Synthetic Genetic Polymers Capable of Heredity and Evolution
It is shown that genetic information can be stored in and recovered from six alternative genetic polymers based on simple nucleic acid architectures not found in nature [xeno-nucleic acids (XNAs)] and selected XNA aptamers, which bind their targets with high affinity and specificity, demonstrating that beyond heredity, specific XNAs have the capacity for Darwinian evolution and folding into defined structures.
Polymerase engineering: towards the encoded synthesis of unnatural biopolymers.
DNA is not only a repository of genetic information for life, it is also a unique polymer with remarkable properties: it associates according to well-defined rules, it can be assembled into diverse nanostructures of defined geometry and it can serve as a supramolecular scaffold to arrange chemical groups in space.
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
A Novel Copper-Mediated DNA Base Pair
A new strategy which is based on the metaldependent pairing of two nucleobases is described which would allow the replication of DNA containing novel functional groups and lead to novel polymers with interesting chemical and physical properties.
A ribozyme composed of only two different nucleotides
It is shown that binary informational macromolecules, containing only two different nucleotide subunits, can act as catalysts and that this ribozyme is specific for the formation of biologically relevant 3′,5′-phosphodiester linkages.
A unique fluorescent base analogue for the expansion of the genetic alphabet.
A novel fluorescent purine analogue, 7-(2,2'-bithien-5-yl)-imidazo[4,5-b]pyridine (denoted as Dss), which can be site-specifically incorporated into DNA and RNA by polymerases, opposite its pairing partner, pyrrole-2-carbaldehyde (Pa), in DNA templates.
Solution structure and conformational dynamics of deoxyxylonucleic acids (dXNA): an orthogonal nucleic acid candidate.
The structure in solution and conformational analysis of two self-complementary, fully modified dXNA oligonucleotides, as determined by CD and NMR spectroscopy are presented, providing the initial experimental proof of the structural orthogonality of dXNAs.
The prebiotic evolutionary advantage of transferring genetic information from RNA to DNA
Analysis of the transitional RNA/DNA hybrid duplexes showed that copying RNA into DNA had similar fidelity to RNA replication, so information could be maintained during the genetic takeover.
Understanding nucleic acids using synthetic chemistry.
  • S. Benner
  • Biology
    Accounts of chemical research
  • 2004
This Account describes work done in these laboratories that has used synthetic, physical organic, and biological chemistry to understand the roles played by the nucleobases, sugars, and phosphates of