Synthetic genetic polymers capable of heredity and evolution

By Vitor B. Pinheiro, Alexander I. Taylor, Christopher Cozens, M. Abramov, M. Renders, Su Zhang, J. Chaput, J. Wengel, S. Peak-Chew, S. McLaughlin and 2 more. Science, 2012

640 citations recorded by the source corpus.

Unnatural Bases The genetic basis of all life on the planet is comprised of deoxyribonucleic acid (DNA) with four nitrogenous nucleotide bases, abbreviated to A, G, C, and T. But there are variations on this theme, and Pinheiro et al. (p. 341; see the Perspective by Joyce) describe the directed evolution of unnatural nucleic acid–like genetic polymers. Variant enzymes were developed that efficiently transcribed DNA to anhydrohexitol (HNA), cyclohexenyl (CeNA), locked (LNA), and threofuranosyl (TNA) nuceic acid analogs. Further variant enzymes were developed to reverse-transcribe these analogs back to DNA. Thus, man-made nucleic acid analogs can be designed and selected that have the potential to operate in a way analogous to the natural process of heredity and evolution. Artificial polymers of nucleic acid–like subunits not found in nature can mimic the functions of DNA and RNA. Genetic information storage and processing rely on just two polymers, DNA and RNA, yet whether their role reflects evolutionary history or fundamental functional constraints is currently unknown. With the use of polymerase evolution and design, we show 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)]. We also select 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. Thus, heredity and evolution, two hallmarks of life, are not limited to DNA and RNA but are likely to be emergent properties of polymers capable of information storage.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4d37bdcca77b0bb604d914ae09d5cb0a3a08d804

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In Molecular Biology

1. N. Bertrand
2. N. Kamaly
3. Xiaoyang Xu
4. Jun Wu
5. O. Farokhzad
6. R. Juliano
7. Jean‐François Lutz
8. David R. Liu

Citations in the corpus

• Sequence-Controlled Polymers (2013, methodology): “Using encoded primary structures for data storage is presented in more detail in Box 2, whereas self-replication is described partly in the first section of this review, but can be explored in (65, 66).”
• Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. (2014, background): “Nucleic acid aptamers (Apts) are single-stranded (usually short) oligonucleotides, such as DNA, RNA or modified nucleic acids (xeno-nucleic acids or XNA) [259, 274].”
• The delivery of therapeutic oligonucleotides (2016, background): “In an interesting variant of the nanostructure approach, rolling circle transcription was used to generate RNAs containing multiple siRNA hairpins; these were complexed with short, ligand-modified DNA oligonucleotides to form nucleic acid nanoparticles that were active in cells and in vivo (331).”
• Current approaches in SELEX: An update to aptamer selection technology. (2015, background): “Also aptamers created of XNAswere generated successfully (Pinheiro et al., 2012) that opened new horizons for aptamers with advanced properties.”
• Directed Polymerase Evolution (2013, methodology): “Recently, Ellington and co-workers adapted the approach for in vitro use, employing water-in-oil emulsion to link genotype and phenotype [62].”