Application of Nucleic Acid Frameworks in the Construction of Nanostructures and Cascade Biocatalysts: Recent Progress and Perspective

Abstract

Nucleic acids underlie the storage and retrieval of genetic information literally in all living organisms, and also provide us excellent materials for making artificial nanostructures and scaffolds for constructing multi-enzyme systems with outstanding performance in catalyzing various cascade reactions, due to their highly diverse and yet controllable structures, which are well determined by their sequences. The introduction of unnatural moieties into nucleic acids dramatically increased the diversity of sequences, structures, and properties of the nucleic acids, which undoubtedly expanded the toolbox for making nanomaterials and scaffolds of multi-enzyme systems. In this article, we first introduce the molecular structures and properties of nucleic acids and their unnatural derivatives. Then we summarized representative artificial nanomaterials made of nucleic acids, as well as their properties, functions, and application. We next review recent progress on constructing multi-enzyme systems with nucleic acid structures as scaffolds for cascade biocatalyst. Finally, we discuss the future direction of applying nucleic acid frameworks in the construction of nanomaterials and multi-enzyme molecular machines, with the potential contribution that unnatural nucleic acids may make to this field highlighted.

From polymerase engineering to semi-synthetic life: artificial expansion of the central dogma

“…Although only one atom or group in the pentose is substituted, some of these modifications lead to significant changes of the properties of DNA or RNA. For example, 2'-F and 2'-OMe modifications greatly increase the melting temperatures, the duplex stabilities, and nuclease resistances of the nucleic acids 45 . Replacement of the oxygen in the sugar ring with sulfur leads to the production of 4'-thiol-modified DNA and RNA, which have been prepared and investigated by Matsuda and co-workers 46,47 .…”

“…For example, 2 0 -F and 2 0 -OMe modifications greatly increase the melting temperatures, the duplex stabilities, and nuclease resistances of the nucleic acids. 45 Replacement of the oxygen in the sugar ring with sulfur leads to the production of 4 0 -thiol-modified DNA and RNA, which have been prepared and investigated by Matsuda and co-workers. 46,47 They demonstrated that 4 0 -thiol-modified RNA can be transcribed from a DNA template with 4 0 -thiol-CTP and 4 0 -thiol-UTP by T7 RNAP, and 4 0 -thiol-modified DNA can be efficiently amplified by KOD dash DNAP under appropriate conditions and transcribed by T7 RNAP in vitro and by mammalian RNA polymerases in mammalian cells.…”

“…210,211 Construction of novel biomaterials Biomaterials composed of nucleic acids have been extensively developed and used in numerous applications in recent years, due to their fascinating properties, including high programmability and good biocompatibility. 45 Integration of unnatural nucleic acid components is helpful to further improve the properties, increase the functions and expand the applications of these materials. 14 Introduction of nucleobases modified with functional groups into nucleic acid materials immediately enables the coupling of various molecules onto these materials and thus expands the functionalities of these materials.…”

“…Biomaterials composed of nucleic acids have been extensively developed and used in numerous applications in recent years, due to their fascinating properties, including high programmability and good biocompatibility. 45 Integration of unnatural nucleic acid components is helpful to further improve the properties, increase the functions and expand the applications of these materials. 14 …”

Application of Microfluidics in Detection of Circulating Tumor Cells

“…Due to the high surface area volume ratio, compatible capture and release ability, nanomaterials provide a high collision probability for antibodies and CTCs ( Park et al, 2017 ; Wu C. et al, 2019 ; Shi et al, 2022 ; Yi et al, 2022 ; Liu et al, 2022 ; Liu J. et al, 2021 ), which can help improve the sensitivity and specificity of capture, and have attracted extensive attention in the separation of CTCs ( Wongkaew et al, 2018 ; Wu and Qu, 2015 ; Zhu G. et al, 2021 ; Naskar et al, 2020 ; Chandankere et al, 2020 ). So far, carbon nanotubes (CNTs) ( Cho H. et al, 2018 ; Zhang P. et al, 2019 ; Poudineh et al, 2017 ), graphene oxide (GO) ( Chen et al, 2012 ; Yoon et al, 2013 ; Yu X. et al, 2013 ; Yoon et al, 2016 ), gold nanoparticles (AuNP) ( Park et al, 2017 ), nanocolumns ( Lin et al, 2014 ; Shi et al, 2022 ) and TiO 2 nanofibers ( Zhang et al, 2012 ) have been widely used in affinity group capture methods ( Zhao et al, 2016 ; Cai et al, 2017 ; Wongkaew et al, 2018 ).…”