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Dear Colleagues,

Nucleic acids have emerged as therapeutics or drug carriers, and demonstrated the potential to treat diseases. Nucleic acid therapeutics such as antisense oligonucleotides and small interfering RNA have shown therapeutic effects. The safe and effective delivery of nucleic acid therapeutics into cells to perform gene therapy via sophisticated delivery platforms is becoming increasing attractive.

Besides therapeutics, nucleic acids have also been used to construct nucleic acid nanostructures for drug delivery owing to their predictability and programmability. Some DNA nanostructures can perform structural transformation in response to stimuli. A wave of the design and use of DNA nanostructures as drug carriers to perform complex tasks such as targeted load delivery and the triggered release of loads in response to stimuli has occurred.

However, knowledge and works in these fields are still limited. To achieve a better understanding and exploration of the nucleic-acid-based therapeutics and nanostructures as drug carriers, papers addressing the following aspects are welcome (note that we use the term ‘nucleic-acid-based drugs’ to include all nucleic-acid-based approaches): 1) new nucleic acid therapeutics, platforms for the delivery of nucleic-acid therapeutics, the rationale and key technological aspects for improving their therapeutic effectiveness, and the technologies facilitating their clinical translation. 2) Studies on various DNA nanostructure-based drug delivery systems—their design strategies; the targeting and stimuli-responsive mechanisms of the platforms; their drug release behaviors; and their disease therapeutic effects.

Dr. Zhenbao Liu
Guest Editor

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Keywords

nucleic acid therapeutics
DNA nanostructure
drug delivery platforms
drug delivery systems
therapeutic effectiveness

Published Papers (3 papers)

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Research

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16 pages, 3929 KiB

Open AccessArticle

Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides

by Timofey D. Zharkov, Oleg V. Markov, Sergey A. Zhukov, Svetlana N. Khodyreva and Maxim S. Kupryushkin

Molecules 2024, 29(2), 452; https://doi.org/10.3390/molecules29020452 - 17 Jan 2024

Viewed by 752

Abstract

Numerous types of oligonucleotide modifications have been developed since automated synthesis of DNA/RNA became a common instrument in the creation of synthetic oligonucleotides. Despite the growing number of types of oligonucleotide modifications under development, only a few of them and, moreover, their combinations have been studied widely enough in terms of their influence on the properties of corresponding NA constructions. In the present study, a number of oligonucleotides with combinations of 3′-end lipophilic (a single cholesteryl or a pair of dodecyl residues) and phosphate backbone modifications were synthesized. The influence of the combination of used lipophilic groups with phosphate modifications of various natures and different positions on the efficiency of cell penetration was evaluated. The obtained results indicate that even a couple of phosphate modifications are able to affect a set of oligonucleotide properties in a complex manner and can remarkably change cellular uptake. These data clearly show that the strategy of using different patterns of modification combinations has great potential for the rational design of oligonucleotide structures with desired predefined properties. Full article

(This article belongs to the Special Issue The Current Landscape of Nucleic-Acid-Based Drugs)

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Graphical abstract

14 pages, 4788 KiB

Open AccessArticle

DNA Origami Disguises Herpes Simplex Virus 1 Particles and Controls Their Virulence

by Raina M. Borum, Avery E. Lin, Xiangyi Dong, Mingxuan Kai and Yi Chen

Molecules 2022, 27(21), 7162; https://doi.org/10.3390/molecules27217162 - 23 Oct 2022

Viewed by 1907

Abstract

DNA nanostructures are well-established vectors for packaging diversified payloads for targeted cellular delivery. Here, DNA origami rectangular sheets were combined with Herpes Simplex Virus 1 (HSV1) capsids to demonstrate surface coverage of the particle via electrostatic interactions. The optimized origami:HSV1 molar ratios led to characteristic packaging geometries ranging from dispersed “HSV1 pockets” to agglomerated “HSV1 sleeves”. “Pockets” were disguised from cells in HeLa and B16F10 cells and were 44.2% less infective than naked HSV1 particles. However, the pockets were 117% more infective than naked HSV1 particles when the origami sheets were coated with folic acid. We observed infectivity from naked origami, but they are 99.1% less infective with respect to HSV1 and 99.6% less infective with respect to the pocket complexes. This work suggests that DNA origami can selectively modulate virus infectivity. Full article

(This article belongs to the Special Issue The Current Landscape of Nucleic-Acid-Based Drugs)

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Review

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18 pages, 3614 KiB

Open AccessReview

DNA-Guided Metallization of Nanomaterials and Their Biomedical Applications

by Ke Li, Yanfei Liu, Beibei Lou, Yifu Tan, Liwei Chen and Zhenbao Liu

Molecules 2023, 28(9), 3922; https://doi.org/10.3390/molecules28093922 - 06 May 2023

Cited by 2 | Viewed by 1812

Abstract

Precise control of the structure of metallic nanomaterials is critical for the advancement of nanobiotechnology. As DNA (deoxyribonucleic acid) can readily modify various moieties, such as sulfhydryl, carboxyl, and amino groups, using DNA as a directing ligand to modulate the morphology of nanomaterials is a promising strategy. In this review, we focus on the use of DNA as a template to control the morphology of metallic nanoparticles and their biomedical applications, discuss the use of DNA for the metallization of gold and silver, explore the factors that influence the process, and outline its biomedical applications. This review aims to provide valuable insights into the DNA-guided growth of nanomaterials. The challenges and future directions are also discussed. Full article

(This article belongs to the Special Issue The Current Landscape of Nucleic-Acid-Based Drugs)

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