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Molecules
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Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy
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Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Nanochemistry".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 54635

Special Issue Editor

Dr. Kirill A. Afonin

E-Mail Website
Guest Editor
Department of Chemistry, UNC Charlotte, Charlotte, NC, USA
Interests: RNA nanobiology; drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immunotherapy describes the treatment of disease using immune cells and immunomodulatory molecules such as certain proteins and nucleic acids. The burgeoning field of immunotherapy has seen tremendous advances in treating complex diseases such as cancers and autoimmune disorders. Recently, nucleic acids have garnered tremendous attention for these purposes due to their precise customizability and varied activities in personalized nanomedicine. Nucleic acids have the ability to act as natural immune suppressants or activators for a variety of purposes. Advancements in aptamer technology, the discovery of regulatory RNAs, and developments in nanotechnology have enabled a myriad of novel therapies based on DNA and RNA.

Immunomodulatory nucleic acids have been identified as potent pharmaceuticals, ranging from Toll-Like Receptor (TLR) agonists to checkpoint blockades. CpG DNA oligonucleotides bind specifically to TLR 9 and act as effective immune activators, generating a far greater immune response than that of random sequence DNAs of the same length. Similarly designed DNA agonists have been shown to bind irreversibly to the same receptors to reduce undesirable immune responses.

By harnessing the programmable architecture of nucleic acids, dynamic structures can be designed which are capable of carrying out precisely controlled functions and immunomodulation for uses in nanomedicine. The coverage of this special issue will include (but not limited) by following topics:

  • Immunorecognition of nucleic acids in animal models and humans
  • Desirable immunomodulation using nucleic-acid based nanoparticles
  • Undesirable immunological side-effects of nucleic acid therapeutics
  • Rational design and characterization of programmable nucleic-acid based nanoparticles
  • Delivery of nucleic-acid based nanoparticles and effect of carrier on their immunorecognition
  • Therapeutic nucleic-acid based nanoparticles: design, assembly, characterization

Dr. Kirill Afonin
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. Molecules is an international peer-reviewed open access semimonthly 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

  • Nuclec acid nanoparticles
  • NANPs
  • Immunorecognition
  • Toll-like receptors
  • Drug delivery
  • Therapeutic Nucleic acids
  • Immune system

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Published Papers (7 papers)

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Research

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14 pages, 2281 KiB  
Article
DNA-Templated Fluorescent Silver Nanoclusters Inhibit Bacterial Growth While Being Non-Toxic to Mammalian Cells
by Lewis Rolband, Liam Yourston, Morgan Chandler, Damian Beasock, Leyla Danai, Seraphim Kozlov, Nolan Marshall, Oleg Shevchenko, Alexey V. Krasnoslobodtsev and Kirill A. Afonin
Molecules 2021, 26(13), 4045; https://doi.org/10.3390/molecules26134045 - 1 Jul 2021
Cited by 20 | Viewed by 4597
Abstract
Silver has a long history of antibacterial effectiveness. The combination of atomically precise metal nanoclusters with the field of nucleic acid nanotechnology has given rise to DNA-templated silver nanoclusters (DNA-AgNCs) which can be engineered with reproducible and unique fluorescent properties and antibacterial activity. [...] Read more.
Silver has a long history of antibacterial effectiveness. The combination of atomically precise metal nanoclusters with the field of nucleic acid nanotechnology has given rise to DNA-templated silver nanoclusters (DNA-AgNCs) which can be engineered with reproducible and unique fluorescent properties and antibacterial activity. Furthermore, cytosine-rich single-stranded DNA oligonucleotides designed to fold into hairpin structures improve the stability of AgNCs and additionally modulate their antibacterial properties and the quality of observed fluorescent signals. In this work, we characterize the sequence-specific fluorescence and composition of four representative DNA-AgNCs, compare their corresponding antibacterial effectiveness at different pH, and assess cytotoxicity to several mammalian cell lines. Full article
(This article belongs to the Special Issue Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy)
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Review

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19 pages, 1080 KiB  
Review
In Vivo Production of RNA Aptamers and Nanoparticles: Problems and Prospects
by Ousama Al Shanaa, Andrey Rumyantsev, Elena Sambuk and Marina Padkina
Molecules 2021, 26(5), 1422; https://doi.org/10.3390/molecules26051422 - 6 Mar 2021
Cited by 4 | Viewed by 5009
Abstract
RNA aptamers are becoming increasingly attractive due to their superior properties. This review discusses the early stages of aptamer research, the main developments in this area, and the latest technologies being developed. The review also highlights the advantages of RNA aptamers in comparison [...] Read more.
RNA aptamers are becoming increasingly attractive due to their superior properties. This review discusses the early stages of aptamer research, the main developments in this area, and the latest technologies being developed. The review also highlights the advantages of RNA aptamers in comparison to antibodies, considering the great potential of RNA aptamers and their applications in the near future. In addition, it is shown how RNA aptamers can form endless 3-D structures, giving rise to various structural and functional possibilities. Special attention is paid to the Mango, Spinach and Broccoli fluorescent RNA aptamers, and the advantages of split RNA aptamers are discussed. The review focuses on the importance of creating a platform for the synthesis of RNA nanoparticles in vivo and examines yeast, namely Saccharomyces cerevisiae, as a potential model organism for the production of RNA nanoparticles on a large scale. Full article
(This article belongs to the Special Issue Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy)
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18 pages, 1895 KiB  
Review
Synthesis of DNA Origami Scaffolds: Current and Emerging Strategies
by Joshua Bush, Shrishti Singh, Merlyn Vargas, Esra Oktay, Chih-Hsiang Hu and Remi Veneziano
Molecules 2020, 25(15), 3386; https://doi.org/10.3390/molecules25153386 - 26 Jul 2020
Cited by 35 | Viewed by 11559
Abstract
DNA origami nanocarriers have emerged as a promising tool for many biomedical applications, such as biosensing, targeted drug delivery, and cancer immunotherapy. These highly programmable nanoarchitectures are assembled into any shape or size with nanoscale precision by folding a single-stranded DNA scaffold with [...] Read more.
DNA origami nanocarriers have emerged as a promising tool for many biomedical applications, such as biosensing, targeted drug delivery, and cancer immunotherapy. These highly programmable nanoarchitectures are assembled into any shape or size with nanoscale precision by folding a single-stranded DNA scaffold with short complementary oligonucleotides. The standard scaffold strand used to fold DNA origami nanocarriers is usually the M13mp18 bacteriophage’s circular single-stranded DNA genome with limited design flexibility in terms of the sequence and size of the final objects. However, with the recent progress in automated DNA origami design—allowing for increasing structural complexity—and the growing number of applications, the need for scalable methods to produce custom scaffolds has become crucial to overcome the limitations of traditional methods for scaffold production. Improved scaffold synthesis strategies will help to broaden the use of DNA origami for more biomedical applications. To this end, several techniques have been developed in recent years for the scalable synthesis of single stranded DNA scaffolds with custom lengths and sequences. This review focuses on these methods and the progress that has been made to address the challenges confronting custom scaffold production for large-scale DNA origami assembly. Full article
(This article belongs to the Special Issue Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy)
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17 pages, 1653 KiB  
Review
Detection of Beta-Glucan Contamination in Nanotechnology-Based Formulations
by Barry W. Neun, Edward Cedrone, Timothy M. Potter, Rachael M. Crist and Marina A. Dobrovolskaia
Molecules 2020, 25(15), 3367; https://doi.org/10.3390/molecules25153367 - 24 Jul 2020
Cited by 15 | Viewed by 7851
Abstract
Understanding the potential contamination of pharmaceutical products with innate immunity modulating impurities (IIMIs) is essential for establishing their safety profiles. IIMIs are a large family of molecules with diverse compositions and structures that contribute to the immune-mediated adverse effects (IMAE) of drug products. [...] Read more.
Understanding the potential contamination of pharmaceutical products with innate immunity modulating impurities (IIMIs) is essential for establishing their safety profiles. IIMIs are a large family of molecules with diverse compositions and structures that contribute to the immune-mediated adverse effects (IMAE) of drug products. Pyrogenicity (the ability to induce fever) and activation of innate immune responses underlying both acute toxicities (e.g., anaphylactoid reactions or pseudoallergy, cytokine storm) and long-term effects (e.g., immunogenicity) are among the IMAE commonly related to IIMI contamination. Endotoxins of gram-negative bacteria are the best-studied IIMIs in that both methodologies for and pitfalls in their detection and quantification are well established. Additionally, regulatory guidance documents and research papers from laboratories worldwide are available on endotoxins. However, less information is currently known about other IIMIs. Herein, we focus on one such IIMI, namely, beta-glucans, and review literature and discuss the experience of the Nanotechnology Characterization Lab (NCL) with the detection of beta-glucans in nanotechnology-based drug products. Full article
(This article belongs to the Special Issue Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy)
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26 pages, 3447 KiB  
Review
Gold Nanoparticles in Conjunction with Nucleic Acids as a Modern Molecular System for Cellular Delivery
by Anna Graczyk, Roza Pawlowska, Dominika Jedrzejczyk and Arkadiusz Chworos
Molecules 2020, 25(1), 204; https://doi.org/10.3390/molecules25010204 - 3 Jan 2020
Cited by 85 | Viewed by 14766
Abstract
Development of nanotechnology has become prominent in many fields, such as medicine, electronics, production of materials, and modern drugs. Nanomaterials and nanoparticles have gained recognition owing to the unique biochemical and physical properties. Considering cellular application, it is speculated that nanoparticles can transfer [...] Read more.
Development of nanotechnology has become prominent in many fields, such as medicine, electronics, production of materials, and modern drugs. Nanomaterials and nanoparticles have gained recognition owing to the unique biochemical and physical properties. Considering cellular application, it is speculated that nanoparticles can transfer through cell membranes following different routes exclusively owing to their size (up to 100 nm) and surface functionalities. Nanoparticles have capacity to enter cells by themselves but also to carry other molecules through the lipid bilayer. This quality has been utilized in cellular delivery of substances like small chemical drugs or nucleic acids. Different nanoparticles including lipids, silica, and metal nanoparticles have been exploited in conjugation with nucleic acids. However, the noble metal nanoparticles create an alternative, out of which gold nanoparticles (AuNP) are the most common. The hybrids of DNA or RNA and metal nanoparticles can be employed for functional assemblies for variety of applications in medicine, diagnostics or nano-electronics by means of biomarkers, specific imaging probes, or gene expression regulatory function. In this review, we focus on the conjugates of gold nanoparticles and nucleic acids in the view of their potential application for cellular delivery and biomedicine. This review covers the current advances in the nanotechnology of DNA and RNA-AuNP conjugates and their potential applications. We emphasize the crucial role of metal nanoparticles in the nanotechnology of nucleic acids and explore the role of such conjugates in the biological systems. Finally, mechanisms guiding the process of cellular intake, essential for delivery of modern therapeutics, will be discussed. Full article
(This article belongs to the Special Issue Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy)
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20 pages, 2542 KiB  
Review
Nucleic Acid Nanoparticles at a Crossroads of Vaccines and Immunotherapies
by Marina A. Dobrovolskaia
Molecules 2019, 24(24), 4620; https://doi.org/10.3390/molecules24244620 - 17 Dec 2019
Cited by 22 | Viewed by 5794
Abstract
Vaccines and immunotherapies involve a variety of technologies and act through different mechanisms to achieve a common goal, which is to optimize the immune response against an antigen. The antigen could be a molecule expressed on a pathogen (e.g., a disease-causing bacterium, a [...] Read more.
Vaccines and immunotherapies involve a variety of technologies and act through different mechanisms to achieve a common goal, which is to optimize the immune response against an antigen. The antigen could be a molecule expressed on a pathogen (e.g., a disease-causing bacterium, a virus or another microorganism), abnormal or damaged host cells (e.g., cancer cells), environmental agent (e.g., nicotine from a tobacco smoke), or an allergen (e.g., pollen or food protein). Immunogenic vaccines and therapies optimize the immune response to improve the eradication of the pathogen or damaged cells. In contrast, tolerogenic vaccines and therapies retrain or blunt the immune response to antigens, which are recognized by the immune system as harmful to the host. To optimize the immune response to either improve the immunogenicity or induce tolerance, researchers employ different routes of administration, antigen-delivery systems, and adjuvants. Nanocarriers and adjuvants are of particular interest to the fields of vaccines and immunotherapy as they allow for targeted delivery of the antigens and direct the immune response against these antigens in desirable direction (i.e., to either enhance immunogenicity or induce tolerance). Recently, nanoparticles gained particular attention as antigen carriers and adjuvants. This review focuses on a particular subclass of nanoparticles, which are made of nucleic acids, so-called nucleic acid nanoparticles or NANPs. Immunological properties of these novel materials and considerations for their clinical translation are discussed. Full article
(This article belongs to the Special Issue Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy)
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Graphical abstract

13 pages, 15406 KiB  
Review
Modulating Immune Response with Nucleic Acid Nanoparticles
by Jake K. Durbin, Daniel K. Miller, Julia Niekamp and Emil F. Khisamutdinov
Molecules 2019, 24(20), 3740; https://doi.org/10.3390/molecules24203740 - 17 Oct 2019
Cited by 13 | Viewed by 4051
Abstract
Nano-objects made of nucleic acids are becoming promising materials in the biomedical field. This is, in part, due to DNA and RNA self-assembly properties that can be accurately computed to fabricate various complex nanoarchitectures of 2D and 3D shapes. The nanoparticles can be [...] Read more.
Nano-objects made of nucleic acids are becoming promising materials in the biomedical field. This is, in part, due to DNA and RNA self-assembly properties that can be accurately computed to fabricate various complex nanoarchitectures of 2D and 3D shapes. The nanoparticles can be assembled from DNA, RNA, and chemically modified oligonucleotide mixtures which, in turn, influence their chemical and biophysical properties. Solid-phase synthesis allows large-scale production of individual oligonucleotide strands with batch-to-batch consistency and exceptional purity. All of these advantageous characteristics of nucleic-acid-based nanoparticles were known to be exceptionally useful as a nanoplatform for drug delivery purposes. Recently, several important discoveries have been achieved, demonstrating that nucleic acid nanoparticles (NANPs) can also be used to modulate the immune response of host cells. The purpose of this review is to briefly overview studies demonstrating architectural design principles of NANPs, as well as the ability of NANPs to control immune responses. Full article
(This article belongs to the Special Issue Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy)
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