Bioorthogonal information storage in l-DNA with a high-fidelity mirror-image Pfu DNA polymerase

Fan, Chuyao; Deng, Qiang; Zhu, Ting

doi:10.1038/s41587-021-00969-6

Cited by 59 publications

(72 citation statements)

References 63 publications

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“…It usually goes without saying that the polymerase enzyme and the DNA or RNA being amplified are of the usual biological handedness; that is, the protein is composed of l -amino acids and the nucleic acid is composed of d -nucleotides. It is understood that if the mirror were reversed, the result would be equivalent, and there are examples in which a chemically synthesized polymerase protein composed of d -amino acids has been shown to synthesize, and even amplify, nucleic acids composed of l -nucleotides. − But would it be possible to use a polymerase of the biological chirality to amplify nucleic acids of the nonbiological chirality?…”

Section: Introductionmentioning

confidence: 99%

Cross-Chiral, RNA-Catalyzed Exponential Amplification of RNA

Bare

Joyce

2021

J. Am. Chem. Soc.

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Informational macromolecules in biology are composed of subunits of a single handedness, d-nucleotides in nucleic acids and l-amino acids in proteins. Although this chiral uniformity may be expedient, it is not a chemical necessity, as demonstrated by the recent example of an RNA enzyme that catalyzes the RNA-templated polymerization of RNA molecules of the opposite handedness. This reaction, when carried out iteratively, can provide the basis for exponential amplification of RNA molecules and the information they contain. By carrying out thermal cycling, analogous to the polymerase chain reaction, and supplying oligonucleotide building blocks that comprise both the functional strand of RNA and its complement, cross-chiral exponential amplification was achieved. This process was used to amplify the l-RNA form of the hammerhead ribozyme, catalyzed by the d-RNA form of the polymerase. The resulting l-hammerhead exhibits the expected activity in cleaving a corresponding l-RNA substrate. Exponential amplification was also carried out within individual droplets of a water-in-oil emulsion. The ability to amplify enantio-RNAs, both in bulk solution and within compartments, provides a means to evolve cross-chiral RNA polymerases based on the function of the RNAs they produce.

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Section: Introductionmentioning

confidence: 99%

Cross-Chiral, RNA-Catalyzed Exponential Amplification of RNA

Bare

Joyce

2021

J. Am. Chem. Soc.

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“…After billions of years of evolution, there is a lack of competent polymerases to accurately recognize and readily amplify L -nucleic acids. The efforts are now delivered to engineer non-natural polymerases, either via the chemical syntheses of entirely modified D -polymerases [ 142 , 143 , 144 , 145 ] or through searching for the ancient polymerase, which can interact with both enantiomeric nucleic acids [ 146 ]. It is worth noting, some labs are also focused on developing artificial ribosomes, which contain mutated 23S ribosomal RNA [ 147 , 148 , 149 ].…”

Section: Discussionmentioning

confidence: 99%

Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness

Dantsu

Zhang

2021

Genes

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Nucleic-acid-based small molecule and oligonucleotide therapies are attractive topics due to their potential for effective target of disease-related modules and specific control of disease gene expression. As the non-naturally occurring biomolecules, modified DNA/RNA nucleoside and oligonucleotide analogues composed of L-(deoxy)riboses, have been designed and applied as innovative therapeutics with superior plasma stability, weakened cytotoxicity, and inexistent immunogenicity. Although all the chiral centers in the backbone are mirror converted from the natural D-nucleic acids, L-nucleic acids are equipped with the same nucleobases (A, G, C and U or T), which are critical to maintain the programmability and form adaptable tertiary structures for target binding. The types of L-nucleic acid drugs are increasingly varied, from chemically modified nucleoside analogues that interact with pathogenic polymerases to nanoparticles containing hundreds of repeating L-nucleotides that circulate durably in vivo. This article mainly reviews three different aspects of L-nucleic acid therapies, including pharmacological L-nucleosides, Spiegelmers as specific target-binding aptamers, and L-nanostructures as effective drug-delivery devices.

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“…The biological inactivity of the L-form lends itself to the study of inhibition of 2dDR-mediated functions, for example, the L-form inhibits the protection afforded by 2dDR against hypoxic-mediated apoptosis via interaction with thymidine phosphorylase [ 37 ]. While the D-form of 2dDR is a precursor for DNA synthesis, the L-form is used to create L-DNA (mirror DNA), which can store information identical to normal DNA but is resistant to biodegradation [ 42 ].…”

Section: What Do We Understand Of the Mechanism Of Action Of 2ddr? How Does Sugar Structure Affect Function?mentioning

confidence: 99%

Developing Wound Dressings Using 2-deoxy-D-Ribose to Induce Angiogenesis as a Backdoor Route for Stimulating the Production of Vascular Endothelial Growth Factor

Dikici

Yar

Bullock

et al. 2021

IJMS

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2-deoxy-D-Ribose (2dDR) was first identified in 1930 in the structure of DNA and discovered as a degradation product of it later when the enzyme thymidine phosphorylase breaks down thymidine into thymine. In 2017, our research group explored the development of wound dressings based on the delivery of this sugar to induce angiogenesis in chronic wounds. In this review, we will survey the small volume of conflicting literature on this and related sugars, some of which are reported to be anti-angiogenic. We review the evidence of 2dDR having the ability to stimulate a range of pro-angiogenic activities in vitro and in a chick pro-angiogenic bioassay and to stimulate new blood vessel formation and wound healing in normal and diabetic rat models. The biological actions of 2dDR were found to be 80 to 100% as effective as VEGF in addition to upregulating the production of VEGF. We then demonstrated the uptake and delivery of the sugar from a range of experimental and commercial dressings. In conclusion, its pro-angiogenic properties combined with its improved stability on storage compared to VEGF, its low cost, and ease of incorporation into a range of established wound dressings make 2dDR an attractive alternative to VEGF for wound dressing development.

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Bioorthogonal information storage in l-DNA with a high-fidelity mirror-image Pfu DNA polymerase

Cited by 59 publications

References 63 publications

Cross-Chiral, RNA-Catalyzed Exponential Amplification of RNA

Cross-Chiral, RNA-Catalyzed Exponential Amplification of RNA

Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness

Developing Wound Dressings Using 2-deoxy-D-Ribose to Induce Angiogenesis as a Backdoor Route for Stimulating the Production of Vascular Endothelial Growth Factor

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