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Designed and Evolved Nucleic Acid Nanotechnology: Contrast and Complementarity.

ABSTRACT: In this review, we explore progress on DNA aptamers (evolved DNA), DNA circuits (designed DNA), and the newest projects that integrate both. Designed DNA nanotechnology includes static nanostructures, dynamic nanodevices, and reaction networks (sometimes called DNA circuits). DNA circuits are dynamic DNA reactions that perform computations and sequence-specific amplification. Directed evolution can be used to produce DNA that can recognize specific targets. Aptamers are evolved nucleic acids; they are produced artificially with an in vitro selection process. DNA aptamers are molecular recognition elements made of single-stranded DNA (ssDNA) with the potential to interact with proteins, small molecules, viruses, and even cells. Designed molecular structures can incorporate aptamers for applications with immediate practical impact.

SUBMITTER: Damase TR

PROVIDER: S-EPMC6938684 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Designed and Evolved Nucleic Acid Nanotechnology: Contrast and Complementarity.

Damase Tulsi Ram TR Allen Peter B PB

Bioconjugate chemistry 20190103 1

In this review, we explore progress on DNA aptamers (evolved DNA), DNA circuits (designed DNA), and the newest projects that integrate both. Designed DNA nanotechnology includes static nanostructures, dynamic nanodevices, and reaction networks (sometimes called DNA circuits). DNA circuits are dynamic DNA reactions that perform computations and sequence-specific amplification. Directed evolution can be used to produce DNA that can recognize specific targets. Aptamers are evolved nucleic acids; th ...[more]

PMID: 30561987

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Project description:Biochemical strategies that use a combination of synthetic oligonucleotides, thermostable DNA polymerases, and DNA ligases can produce large DNA constructs up to 1 megabase in length. Although these ambitious targets are feasible biochemically, comparable technologies for the chemical synthesis of long DNA strands lag far behind. The best available chemical approach is the solid-phase phosphoramidite method, which can be used to assemble DNA strands up to 150 bases in length. Beyond this point, deficiencies in the chemistry make it impossible to produce pure DNA. A possible alternative approach to the chemical synthesis of large DNA strands is to join together carefully purified synthetic oligonucleotides by chemical methods. Click ligation by the copper-catalyzed azide-alkyne (CuAAC) reaction could facilitate this process. In this Account, we describe the synthesis, characterization, and applications of oligonucleotides prepared by click ligation. The alkyne and azide oligonucleotide strands can be prepared by standard protocols, and the ligation reaction is compatible with a wide range of chemical modifications to DNA and RNA. We have employed click ligation to synthesize DNA constructs up to 300 bases in length and much longer sequences are feasible. When the resulting triazole linkage is placed in a PCR template, various DNA polymerases correctly copy the entire base sequence. We have also successfully demonstrated both in vitro transcription and rolling circle amplification through the modified linkage. This linkage has shown in vivo biocompatibility: an antibiotic resistance gene containing triazole linkages functions in E. coli . Using click ligation, we have synthesized hairpin ribozymes up to 100 nucleotides in length and a hammerhead ribozyme with the triazole linkage located at the substrate cleavage site. At the opposite end of the length scale, click-ligated, cyclic mini-DNA duplexes have been used as models to study base pairing. Cyclic duplexes have potential therapeutic applications. They have extremely high thermodynamic stability, have increased resistance to enzymatic degradation, and have been investigated as decoys for regulatory proteins. For potential nanotechnology applications, we have synthesized double stranded DNA catenanes by click ligation. Other researchers have studied covalently fixed multistranded DNA constructs including triplexes and quadruplexes.

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Designed and Evolved Nucleic Acid Nanotechnology: Contrast and Complementarity.

Publications

Designed and Evolved Nucleic Acid Nanotechnology: Contrast and Complementarity.

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