Development of Nucleic Acid Delivery System

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 20 September 2024 | Viewed by 14683

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Guest Editor
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Interests: nano drug delivery systems; nucleic acid delivery; controlled release systems; targeted drug delivery
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Special Issue Information

Dear Colleagues,

With the technological development of gene therapy, the RNA interference, gene editing and mRNA therapy, therapeutic nucleic acids are increasingly being developed for the treatment of various diseases, including plasmid DNA, small interfering RNA (siRNA), mRNA, etc. These therapeutic nucleic acid molecules belong to biological macromolecules, and their efficiency of uptake and absorption by cells is very low, which impacts their efficacy. Moreover, these nucleic acid molecules are easy to degrade in vivo, so there is an urgent need for in vivo protection and delivery by vectors. In early-stage gene therapy, researchers develop a variety of recombinant virus vectors, which can carry therapeutic gene fragments, infect cells and regulate gene expression in cells. However, recombinant virus vectors still have side effects, such as an immune response and mutagenicity in vivo, which have limited the development of clinical applications of gene therapy. The side effects of viral vectors directly promote researchers to search for nonviral delivery vectors in the field of chemical materials to achieve the efficient delivery of plasmid DNA. With the development of functional materials, increasingly more advanced nonviral nucleic acid delivery vectors have been developed, such as active-targeting vectors, stimuli-responsive vectors, etc. These vectors play a key role in the protection and delivery of nucleic acids in the therapy of plasmid DNA, siRNA and mRNA. It is worth mentioning that lipid nanoparticles play a vital role as mRNA delivery vectors in the clinical application of anti-COVID-19 mRNA vaccines. Although there are many kinds of nucleic acid delivery vectors, there are few examples that can deliver mRNA in the same way as lipid nanoparticles and convert it into clinical therapeutic products. In the field of nucleic acid delivery, the development of safe and efficient delivery vectors that can be transformed into clinical products has always been an eternal hot spot and difficulty, requiring us to further explore this research field. Therefore, we would like to invite you to provide reviews and original articles focusing on the latest progress in therapeutic nucleic acid delivery systems, which will be published as part of the Special Issue entitled "Development of Nucleic Acid Delivery System". Special topics include, but are not limited to: nucleic acid delivery system, nonviral vectors, gene delivery, siRNA delivery, gene-editing system delivery, mRNA delivery, codelivery of small-molecule drugs and nucleic acids, the clinical transformation of nucleic acid delivery systems, etc.

We look forward to your contribution.

Dr. Wei Huang
Guest Editor

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Keywords

  • nucleic acid delivery system
  • nonviral vectors
  • gene delivery
  • siRNA delivery
  • gene editing system delivery
  • mRNA delivery
  • codelivery of small-molecule drugs and nucleic acids
  • clinical transformation of nucleic acid delivery systems

Published Papers (4 papers)

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Research

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21 pages, 4161 KiB  
Article
Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo
by Marco Hoffmann, Sven Gerlach, Masanari Takamiya, Samar Tarazi, Nils Hersch, Agnes Csiszár, Ronald Springer, Georg Dreissen, Hanno Scharr, Sepand Rastegar, Tanja Beil, Uwe Strähle, Rudolf Merkel and Bernd Hoffmann
Pharmaceutics 2023, 15(4), 1210; https://doi.org/10.3390/pharmaceutics15041210 - 11 Apr 2023
Cited by 2 | Viewed by 1863
Abstract
The efficient and biocompatible transfer of nucleic acids into mammalian cells for research applications or medical purposes is a long-standing, challenging task. Viral transduction is the most efficient transfer system, but often entails high safety levels for research and potential health impairments for [...] Read more.
The efficient and biocompatible transfer of nucleic acids into mammalian cells for research applications or medical purposes is a long-standing, challenging task. Viral transduction is the most efficient transfer system, but often entails high safety levels for research and potential health impairments for patients in medical applications. Lipo- or polyplexes are commonly used transfer systems but result in comparably low transfer efficiencies. Moreover, inflammatory responses caused by cytotoxic side effects were reported for these transfer methods. Often accountable for these effects are various recognition mechanisms for transferred nucleic acids. Using commercially available fusogenic liposomes (Fuse-It-mRNA), we established highly efficient and fully biocompatible transfer of RNA molecules for in vitro as well as in vivo applications. We demonstrated bypassing of endosomal uptake routes and, therefore, of pattern recognition receptors that recognize nucleic acids with high efficiency. This may underlie the observed almost complete abolishment of inflammatory cytokine responses. RNA transfer experiments into zebrafish embryos and adult animals fully confirmed the functional mechanism and the wide range of applications from single cells to organisms. Full article
(This article belongs to the Special Issue Development of Nucleic Acid Delivery System)
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21 pages, 4152 KiB  
Article
Modified Stability of microRNA-Loaded Nanoparticles
by Katja Fresacher-Scheiber, Ivana Ruseska, Henrik Siboni, Martin Reiser, Fabio Falsone, Leonhard Grill and Andreas Zimmer
Pharmaceutics 2022, 14(9), 1829; https://doi.org/10.3390/pharmaceutics14091829 - 30 Aug 2022
Cited by 1 | Viewed by 1793
Abstract
microRNAs represent promising drugs to treat and prevent several diseases, such as diabetes mellitus. microRNA delivery brings many obstacles to overcome, and one strategy to bypass them is the manufacturing of self-assembled microRNA protein nanoparticles. In this work, a microRNA was combined with [...] Read more.
microRNAs represent promising drugs to treat and prevent several diseases, such as diabetes mellitus. microRNA delivery brings many obstacles to overcome, and one strategy to bypass them is the manufacturing of self-assembled microRNA protein nanoparticles. In this work, a microRNA was combined with the cell-penetrating peptide protamine, forming so-called proticles. Previous studies demonstrated a lack of microRNA dissociation from proticles. Therefore, the goal of this study was to show the success of functionalizing binary proticles with citric acid in order to reduce the binding strength between the microRNA and protamine and further enable sufficient dissociation. Thus, we outline the importance of the present protons provided by the acid in influencing colloidal stability, achieving a constant particle size, and monodispersing the particle size distribution. The use of citric acid also provoked an increase in drug loading. Against all expectations, the AFM investigations demonstrated that our nanoparticles were loose complexes mainly consisting of water, and the addition of citric acid led to a change in shape. Moreover, a successful reduction in binding affinity and nanoparticulate stability are highlighted. Low cellular toxicity and a constant cellular uptake are demonstrated, and as uptake routes, active and passive pathways are discussed. Full article
(This article belongs to the Special Issue Development of Nucleic Acid Delivery System)
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Review

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25 pages, 3102 KiB  
Review
Research Advances in Nucleic Acid Delivery System for Rheumatoid Arthritis Therapy
by Xintong Zhang, Yanhong Liu, Congcong Xiao, Youyan Guan, Zhonggao Gao and Wei Huang
Pharmaceutics 2023, 15(4), 1237; https://doi.org/10.3390/pharmaceutics15041237 - 13 Apr 2023
Cited by 2 | Viewed by 1666
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the lives of nearly 1% of the total population worldwide. With the understanding of RA, more and more therapeutic drugs have been developed. However, lots of them possess severe side effects, and [...] Read more.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the lives of nearly 1% of the total population worldwide. With the understanding of RA, more and more therapeutic drugs have been developed. However, lots of them possess severe side effects, and gene therapy may be a potential method for RA treatment. A nanoparticle delivery system is vital for gene therapy, as it can keep the nucleic acids stable and enhance the efficiency of transfection in vivo. With the development of materials science, pharmaceutics and pathology, more novel nanomaterials and intelligent strategies are applied to better and safer gene therapy for RA. In this review, we first summarized the existing nanomaterials and active targeting ligands used for RA gene therapy. Then, we introduced various gene delivery systems for RA treatment, which may enlighten the relevant research in the future. Full article
(This article belongs to the Special Issue Development of Nucleic Acid Delivery System)
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44 pages, 2895 KiB  
Review
Recent Advances in Lipid Nanoparticles for Delivery of mRNA
by Lei Yang, Liming Gong, Ping Wang, Xinghui Zhao, Feng Zhao, Zhijie Zhang, Yunfei Li and Wei Huang
Pharmaceutics 2022, 14(12), 2682; https://doi.org/10.3390/pharmaceutics14122682 - 1 Dec 2022
Cited by 20 | Viewed by 8337
Abstract
Messenger RNA (mRNA), which is composed of ribonucleotides that carry genetic information and direct protein synthesis, is transcribed from a strand of DNA as a template. On this basis, mRNA technology can take advantage of the body’s own translation system to express proteins [...] Read more.
Messenger RNA (mRNA), which is composed of ribonucleotides that carry genetic information and direct protein synthesis, is transcribed from a strand of DNA as a template. On this basis, mRNA technology can take advantage of the body’s own translation system to express proteins with multiple functions for the treatment of various diseases. Due to the advancement of mRNA synthesis and purification, modification and sequence optimization technologies, and the emerging lipid nanomaterials and other delivery systems, mRNA therapeutic regimens are becoming clinically feasible and exhibit significant reliability in mRNA stability, translation efficiency, and controlled immunogenicity. Lipid nanoparticles (LNPs), currently the leading non-viral delivery vehicles, have made many exciting advances in clinical translation as part of the COVID-19 vaccines and therefore have the potential to accelerate the clinical translation of gene drugs. Additionally, due to their small size, biocompatibility, and biodegradability, LNPs can effectively deliver nucleic acids into cells, which is particularly important for the current mRNA regimens. Therefore, the cutting-edge LNP@mRNA regimens hold great promise for cancer vaccines, infectious disease prevention, protein replacement therapy, gene editing, and rare disease treatment. To shed more lights on LNP@mRNA, this paper mainly discusses the rational of choosing LNPs as the non-viral vectors to deliver mRNA, the general rules for mRNA optimization and LNP preparation, and the various parameters affecting the delivery efficiency of LNP@mRNA, and finally summarizes the current research status as well as the current challenges. The latest research progress of LNPs in the treatment of other diseases such as oncological, cardiovascular, and infectious diseases is also given. Finally, the future applications and perspectives for LNP@mRNA are generally introduced. Full article
(This article belongs to the Special Issue Development of Nucleic Acid Delivery System)
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