Synthetic genetic polymers: advances and applications

Abstract

Advances and applications of synthetic genetic polymers (xeno-nucleic acids) are reviewed in this article. The types of synthetic genetic polymers are summarized. The basic properties of them are elaborated and their technical applications are presented. Challenges and prospects of synthetic genetic polymers are discussed.

Evaluating the effect of ionic strength on PNA:DNA duplex formation kinetics

“…To mitigate this issue, researchers have attempted to improve the stability of natural nucleic acids through substitutions or modifications of the native phosphodiester and sugar backbone. [5][6][7] These synthetic biological polymers, or xeno nucleic acids (XNAs), often offer significant stability advantages over natural nucleic acids, and some offer additional benefits including enhanced duplex thermostability, parallel information systems, and unique secondary structures. While numerous types of XNAs have been reported, peptide nucleic acid (PNA) is one of the most commonly used and studied XNAs due to its nuclease resistance, strong hybridization with natural oligonucleotides, and highly modifiable structure.…”

Genetically Encodable Scaffolds for Optimizing Enzyme Function

“…As such, the use of RNA scaffolds for enzyme tethering has been largely restricted to in vivo applications. The sizable library of RNA aptamers that bind to protein domains, mostly with moderate affinities ( K D —mM–µM), has been critical for creating enzyme pathways in microbial hosts [ 147 ]. To construct an RNA scaffold capable of supporting coupled enzyme catalysis, aptamer-binding protein domains were fused to the enzymes [FeFe]-hydrogenase and ferredoxin.…”

“…Incorporation of ncAA or non-canonical nucleotides (ncNT) into the enzyme and scaffold allows bioorthogonal crosslinking reactions to occur intracellularly [ 144 ]. A widely used coupling reaction used is the Huisgen cycloaddition between the azido and alkynyl functional groups, termed the “click” reaction due to its robustness [ 144 , 147 ]. However, genetic incorporation of ncAA requires engineering/evolution of a tRNA synthetase that specifically loads a chosen ncAA onto a suppressor tRNA, while incorporation of ncNT into an oligomer similarly requires tailoring of DNA polymerases [ 144 , 158 , 159 ].…”

Non-covalent Methods of Engineering Optical Sensors Based on Single-Walled Carbon Nanotubes

“…Due to their modularity, nucleic acids can be readily adjusted using a variety of chemical modifications (Pinheiro and Holliger, 2012; Pinheiro et al, 2013; Ghosh and Chakrabarti, 2016; Ma et al, 2016), and XNAs can contain modifications to either the nucleobase, phosphate, or sugar in an otherwise native oligonucleotide sequence (Pinheiro et al, 2013; Pinheiro and Holliger, 2014; Anosova et al, 2016). Although XNAs were initially developed to emulate the DNA replication processes found in nature, these synthetic oligomers were quickly realized for their advantages in in vivo stability and specificity (Wang et al, 2005; Pinheiro and Holliger, 2014; Taylor et al, 2014; Ma et al, 2016). Larger base modifications can result in altered physico-chemical properties, such as a tendency to adopt non-standard helical conformations, but certain chemical modifications to the N7 (in purines) or C5 (in pyrimidines), sites that extend into the major DNA groove, can be reasonably tolerated without significant steric impact (Pinheiro and Holliger, 2012).…”