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Biomolecules
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Nucleic Acids: Applications in the Fields of Diagnostics, Therapeutics, Synthetic...
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Nucleic Acids: Applications in the Fields of Diagnostics, Therapeutics, Synthetic Biology, and Beyond

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 36908

Special Issue Editor

Prof. Dr. Anthony J. Berdis

E-Mail Website1 Website2
Guest Editor
Department of Chemistry, SI316, Cleveland State University, 2351 Euclid Avenue, Cleveland, OH 44115, USA
Interests: DNA polymerases; DNA damage; mutagenesis; chemotherapy; cancer biology; synthetic biology; nucleoside analogs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The central dogma of molecular biology, formally postulated in 1957 by Francis Crick, proposes that the flow of genetic information in a typical organism proceeds from DNA, the genetic blueprint, to RNA, the messenger, which is then ultimately processed by ribosomes to produce a specific protein as the functional end-product. Over 60 years later, it is now recognized that RNA and DNA both play much more dynamic roles than originally proposed by Crick. For example, seminal discoveries in RNA interference and CRISPR technologies have paved the way for developing more efficient methodologies to understand how the gene expression affects cellular homeostasis, in order to potentially generate various pathological conditions.  

In this Special Issue, we aim to explore the numerous applications of nucleic acids in areas encompassing diagnostics, therapeutics, synthetic biology, and other exciting areas in the chemistry and biology of DNA and RNA. We are proud to have gathered leading experts in each of these fields so as to provide up-to-date reviews in these important areas. 

Prof. Anthony J. Berdis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Nucleic acid metabolism
  • Diagnostic markers
  • Gene expression
  • Therapeutic agents
  • Synthetic biology

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Published Papers (6 papers)

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Editorial

Jump to: Research, Review

3 pages, 149 KiB  
Editorial
Reimagining the Power of Nucleic Acids as Therapeutic and Diagnostic Agents
by Anthony Berdis
Biomolecules 2021, 11(11), 1707; https://doi.org/10.3390/biom11111707 - 17 Nov 2021
Viewed by 1388
Abstract
The central dogma of molecular biology proposes that in a typical cell, the flow of genetic information proceeds from DNA to RNA to polypeptide [...] Full article
(This article belongs to the Special Issue Nucleic Acids: Applications in the Fields of Diagnostics, Therapeutics, Synthetic Biology, and Beyond)

Research

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16 pages, 3974 KiB  
Article
Design and Evaluation of Synthetic RNA-Based Incoherent Feed-Forward Loop Circuits
by Seongho Hong, Dohyun Jeong, Jordan Ryan, Mathias Foo, Xun Tang and Jongmin Kim
Biomolecules 2021, 11(8), 1182; https://doi.org/10.3390/biom11081182 - 10 Aug 2021
Cited by 13 | Viewed by 5064
Abstract
RNA-based regulators are promising tools for building synthetic biological systems that provide a powerful platform for achieving a complex regulation of transcription and translation. Recently, de novo-designed synthetic RNA regulators, such as the small transcriptional activating RNA (STAR), toehold switch (THS), and three-way [...] Read more.
RNA-based regulators are promising tools for building synthetic biological systems that provide a powerful platform for achieving a complex regulation of transcription and translation. Recently, de novo-designed synthetic RNA regulators, such as the small transcriptional activating RNA (STAR), toehold switch (THS), and three-way junction (3WJ) repressor, have been utilized to construct RNA-based synthetic gene circuits in living cells. In this work, we utilized these regulators to construct type 1 incoherent feed-forward loop (IFFL) circuits in vivo and explored their dynamic behaviors. A combination of a STAR and 3WJ repressor was used to construct an RNA-only IFFL circuit. However, due to the fast kinetics of RNA–RNA interactions, there was no significant timescale difference between the direct activation and the indirect inhibition, that no pulse was observed in the experiments. These findings were confirmed with mechanistic modeling and simulation results for a wider range of conditions. To increase delay in the inhibition pathway, we introduced a protein synthesis process to the circuit and designed an RNA–protein hybrid IFFL circuit using THS and TetR protein. Simulation results indicated that pulse generation could be achieved with this RNA–protein hybrid model, and this was further verified with experimental realization in E. coli. Our findings demonstrate that while RNA-based regulators excel in speed as compared to protein-based regulators, the fast reaction kinetics of RNA-based regulators could also undermine the functionality of a circuit (e.g., lack of significant timescale difference). The agreement between experiments and simulations suggests that the mechanistic modeling can help debug issues and validate the hypothesis in designing a new circuit. Moreover, the applicability of the kinetic parameters extracted from the RNA-only circuit to the RNA–protein hybrid circuit also indicates the modularity of RNA-based regulators when used in a different context. We anticipate the findings of this work to guide the future design of gene circuits that rely heavily on the dynamics of RNA-based regulators, in terms of both modeling and experimental realization. Full article
(This article belongs to the Special Issue Nucleic Acids: Applications in the Fields of Diagnostics, Therapeutics, Synthetic Biology, and Beyond)
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Review

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28 pages, 1784 KiB  
Review
Therapy Approaches for Stargardt Disease
by Elena Piotter, Michelle E McClements and Robert E MacLaren
Biomolecules 2021, 11(8), 1179; https://doi.org/10.3390/biom11081179 - 9 Aug 2021
Cited by 31 | Viewed by 10121
Abstract
Despite being the most prevalent cause of inherited blindness in children, Stargardt disease is yet to achieve the same clinical trial success as has been achieved for other inherited retinal diseases. With an early age of onset and continual progression of disease over [...] Read more.
Despite being the most prevalent cause of inherited blindness in children, Stargardt disease is yet to achieve the same clinical trial success as has been achieved for other inherited retinal diseases. With an early age of onset and continual progression of disease over the life course of an individual, Stargardt disease appears to lend itself to therapeutic intervention. However, the aetiology provides issues not encountered with the likes of choroideremia and X-linked retinitis pigmentosa and this has led to a spectrum of treatment strategies that approach the problem from different aspects. These include therapeutics ranging from small molecules and anti-sense oligonucleotides to viral gene supplementation and cell replacement. The advancing development of CRISPR-based molecular tools is also likely to contribute to future therapies by way of genome editing. In this we review, we consider the most recent pre-clinical and clinical trial data relating to the different strategies being applied to the problem of generating a treatment for the large cohort of Stargardt disease patients worldwide. Full article
(This article belongs to the Special Issue Nucleic Acids: Applications in the Fields of Diagnostics, Therapeutics, Synthetic Biology, and Beyond)
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14 pages, 16589 KiB  
Review
CRISPR as a Diagnostic Tool
by Seohyun Kim, Sangmin Ji and Hye Ran Koh
Biomolecules 2021, 11(8), 1162; https://doi.org/10.3390/biom11081162 - 6 Aug 2021
Cited by 47 | Viewed by 9681
Abstract
Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has recently gained growing attention as a diagnostic tool due to its capability of specific gene targeting. It consists of Cas enzymes and a guide RNA (gRNA) that can cleave the target DNA or RNA [...] Read more.
Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has recently gained growing attention as a diagnostic tool due to its capability of specific gene targeting. It consists of Cas enzymes and a guide RNA (gRNA) that can cleave the target DNA or RNA based on the sequence of the gRNA, making it an attractive genetic engineering technique. In addition to the target-specific binding and cleavage, the trans-cleavage activity was reported for some Cas proteins, including Cas12a and Cas13a, which is to cleave the surrounding single-stranded DNA or RNA upon the target binding of Cas-gRNA complex. All these activities of the CRISPR-Cas system are based on its target-specific binding, making it applied to develop diagnostic methods by detecting the disease-related gene as well as microRNAs and the genetic variations such as single nucleotide polymorphism and DNA methylation. Moreover, it can be applied to detect the non-nucleic acids target such as proteins. In this review, we cover the various CRISPR-based diagnostic methods by focusing on the activity of the CRISPR-Cas system and the form of the target. The CRISPR-based diagnostic methods without target amplification are also introduced briefly. Full article
(This article belongs to the Special Issue Nucleic Acids: Applications in the Fields of Diagnostics, Therapeutics, Synthetic Biology, and Beyond)
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18 pages, 1678 KiB  
Review
Synthetic Biology towards Improved Flavonoid Pharmacokinetics
by Moon Sajid, Chaitanya N. Channakesavula, Shane R. Stone and Parwinder Kaur
Biomolecules 2021, 11(5), 754; https://doi.org/10.3390/biom11050754 - 18 May 2021
Cited by 37 | Viewed by 5586
Abstract
Flavonoids are a structurally diverse class of natural products that have been found to have a range of beneficial activities in humans. However, the clinical utilisation of these molecules has been limited due to their low solubility, chemical stability, bioavailability and extensive intestinal [...] Read more.
Flavonoids are a structurally diverse class of natural products that have been found to have a range of beneficial activities in humans. However, the clinical utilisation of these molecules has been limited due to their low solubility, chemical stability, bioavailability and extensive intestinal metabolism in vivo. Recently, the view has been formed that site-specific modification of flavonoids by methylation and/or glycosylation, processes that occur in plants endogenously, can be used to improve and adapt their biophysical and pharmacokinetic properties. The traditional source of flavonoids and their modified forms is from plants and is limited due to the low amounts present in biomass, intrinsic to the nature of secondary metabolite biosynthesis. Access to greater amounts of flavonoids, and understanding of the impact of modifications, requires a rethink in terms of production, more specifically towards the adoption of plant biosynthetic pathways into ex planta synthesis approaches. Advances in synthetic biology and metabolic engineering, aided by protein engineering and machine learning methods, offer attractive and exciting avenues for ex planta flavonoid synthesis. This review seeks to explore the applications of synthetic biology towards the ex planta biosynthesis of flavonoids, and how the natural plant methylation and glycosylation pathways can be harnessed to produce modified flavonoids with more favourable biophysical and pharmacokinetic properties for clinical use. It is envisaged that the development of viable alternative production systems for the synthesis of flavonoids and their methylated and glycosylated forms will help facilitate their greater clinical application. Full article
(This article belongs to the Special Issue Nucleic Acids: Applications in the Fields of Diagnostics, Therapeutics, Synthetic Biology, and Beyond)
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21 pages, 5385 KiB  
Review
Construction of DNA Biosensors for Mercury (II) Ion Detection Based on Enzyme-Driven Signal Amplification Strategy
by Shuchang Wang
Biomolecules 2021, 11(3), 399; https://doi.org/10.3390/biom11030399 - 8 Mar 2021
Cited by 9 | Viewed by 3749
Abstract
Mercury ion (Hg2+) is a well-known toxic heavy metal ion. It is harmful for human health even at low concentrations in the environment. Therefore, it is very important to measure the level of Hg2+. Many methods, reviewed in several [...] Read more.
Mercury ion (Hg2+) is a well-known toxic heavy metal ion. It is harmful for human health even at low concentrations in the environment. Therefore, it is very important to measure the level of Hg2+. Many methods, reviewed in several papers, have been established on DNA biosensors for detecting Hg2+. However, few reviews on the strategy of enzyme-driven signal amplification have been reported. In this paper, we reviewed this topic by dividing the enzymes into nucleases and DNAzymes according to their chemical nature. Initially, we introduce the nucleases including Exo III, Exo I, Nickase, DSN, and DNase I. In this section, the Exo III-driven signal amplification strategy was described in detail. Because Hg2+ can help ssDNA fold into dsDNA by T-Hg-T, and the substrate of Exo III is dsDNA, Exo III can be used to design Hg2+ biosensor very flexibly. Then, the DNAzyme-assisted signal amplification strategies were reviewed in three categories, including UO22+-specific DNAzymes, Cu2+-specific DNAzymes and Mg2+-specific DNAzymes. In this section, the Mg2+-specific DNAzyme was introduced in detail, because this DNAzyme has highly catalytic activity, and Mg2+ is very common ion which is not harmful to the environment. Finally, the challenges and future perspectives were discussed. Full article
(This article belongs to the Special Issue Nucleic Acids: Applications in the Fields of Diagnostics, Therapeutics, Synthetic Biology, and Beyond)
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