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Pharmaceutics
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Non-viral Gene Delivery Systems, 2nd Edition
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Non-viral Gene Delivery Systems, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: closed (20 July 2023) | Viewed by 20369

Special Issue Editor

Dr. Henrique Faneca

E-Mail Website
Guest Editor
Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
Interests: nanosystems; gene delivery; drug delivery; cancer gene therapy; cancer therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Advances in the field of gene therapy have significantly improved the possibility for nucleic acids as highly promising agents for the treatment of both inherited and acquired human diseases. Substantial progress has been made in the development of different types of nucleic acids, including plasmid DNA, mRNA, microRNA, small interfering RNA, and antisense oligonucleotides. Nevertheless, despite the immense pharmacological potential of these molecules, the successful clinical application of genetic material-based strategies remains dependent on the generation of safe and effective delivery systems that have the ability to overcome the numerous biological barriers associated with gene delivery into target cells.

Until now, the large majority of gene therapy clinical trials have been based on the use of viral vectors, namely, due to features such as high levels of transduction, or efficient and stable integration of exogenous DNA into host genomes. However, several drawbacks have been associated with viral vectors, such as immunogenicity, carcinogenesis, the size limit of exogenous DNA, and the difficulty of large-scale production. Non-viral gene delivery systems have the potential to overcome these limitations, allowing not only a safe but also an efficient gene delivery process into target cells.

This Special Issue has the aim of highlighting the current progress in non-viral gene delivery systems. In this regard, I would like to invite you to submit your original papers or reviews on the design, development, characterization, and application of non-viral gene delivery systems.

Dr. Henrique Faneca
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. Pharmaceutics 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 2900 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

  • non-viral vectors
  • lipid-based systems
  • polymer-based systems
  • gene delivery
  • transfection

Related Special Issue

Published Papers (7 papers)

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Research

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17 pages, 8522 KiB  
Article
Chondrogenic Differentiation of Human Mesenchymal Stem Cells via SOX9 Delivery in Cationic Niosomes
by Natalia Carballo-Pedrares, Clara Sanjurjo-Rodriguez, Jose Señarís, Silvia Díaz-Prado and Ana Rey-Rico
Pharmaceutics 2022, 14(11), 2327; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14112327 - 28 Oct 2022
Cited by 6 | Viewed by 1449
Abstract
Gene transfer to mesenchymal stem cells constitutes a powerful approach to promote their differentiation into the appropriate cartilage phenotype. Although viral vectors represent gold standard vehicles, because of their high efficiency, their use is precluded by important concerns including an elevated immunogenicity and [...] Read more.
Gene transfer to mesenchymal stem cells constitutes a powerful approach to promote their differentiation into the appropriate cartilage phenotype. Although viral vectors represent gold standard vehicles, because of their high efficiency, their use is precluded by important concerns including an elevated immunogenicity and the possibility of insertional mutagenesis. Therefore, the development of new and efficient non-viral vectors is under active investigation. In the present study, we developed new non-viral carriers based on niosomes to promote the effective chondrogenesis of human MSCs. Two different niosome formulations were prepared by varying their composition on non-ionic surfactant, polysorbate 80 solely (P80), or combined with poloxamer 407 (P80PX). The best niosome formulation was proven to transfer a plasmid, encoding for the potent chondrogenic transcription factor SOX9 in hMSC aggregate cultures. Transfection of hMSC aggregates via nioplexes resulted in an increased chondrogenic differentiation with reduced hypertrophy. These results highlight the potential of niosome formulations for gene therapy approaches focused on cartilage repair. Full article
(This article belongs to the Special Issue Non-viral Gene Delivery Systems, 2nd Edition)
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17 pages, 2958 KiB  
Article
Anti-Fibrotic Effect of SDF-1β Overexpression in Bleomycin-Injured Rat Lung
by Kleanthis Fytianos, Ronja Schliep, Sofia Mykoniati, Petra Khan, Katrin E. Hostettler, Michael Tamm, Amiq Gazdhar, Lars Knudsen and Thomas Geiser
Pharmaceutics 2022, 14(9), 1803; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14091803 - 27 Aug 2022
Viewed by 1663
Abstract
Rational: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease and is associated with high mortality due to a lack of effective treatment. Excessive deposition of the extracellular matrix by activated myofibroblasts in the alveolar space leads to scar formation that hinders [...] Read more.
Rational: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease and is associated with high mortality due to a lack of effective treatment. Excessive deposition of the extracellular matrix by activated myofibroblasts in the alveolar space leads to scar formation that hinders gas exchange. Therefore, selectively removing activated myofibroblasts with the aim to repair and remodel fibrotic lungs is a promising approach. Stromal-derived growth factor (SDF-1) is known to stimulate cellular signals which attract stem cells to the site of injury for tissue repair and remodeling. Here, we investigate the effect of overexpression of SDF-1β on lung structure using the bleomycin-injured rat lung model. Methods: Intratracheal administration of bleomycin was performed in adult male rats (F344). Seven days later, in vivo electroporation-mediated gene transfer of either SDF-1β or the empty vector was performed. Animals were sacrificed seven days after gene transfer and histology, design-based stereology, flow cytometry, and collagen measurement were performed on the tissue collected. For in vitro experiments, lung fibroblasts obtained from IPF patients were used. Results: Seven days after SDF-1β gene transfer to bleomycin-injured rat lungs, reduced total collagen, reduced collagen fibrils, improved histology and induced apoptosis of myofibroblasts were observed. Furthermore, it was revealed that TNF-α mediates SDF-1β-induced apoptosis of myofibroblasts; moreover, SDF-1β overexpression increased alveolar epithelial cell numbers and proliferation in vivo and also induced their migration in vitro. Conclusions: Our study demonstrates a new antifibrotic mechanism of SDF-1β overexpression and suggests SDF-1β as a potential new approach for the treatment of lung fibrosis. Full article
(This article belongs to the Special Issue Non-viral Gene Delivery Systems, 2nd Edition)
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27 pages, 5652 KiB  
Article
Amphiphilic Anionic Oligomer-Stabilized Calcium Phosphate Nanoparticles with Prospects in siRNA Delivery via Convection-Enhanced Delivery
by Franziska Mitrach, Maximilian Schmid, Magali Toussaint, Sladjana Dukic-Stefanovic, Winnie Deuther-Conrad, Heike Franke, Alexander Ewe, Achim Aigner, Christian Wölk, Peter Brust, Michael C. Hacker and Michaela Schulz-Siegmund
Pharmaceutics 2022, 14(2), 326; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020326 - 29 Jan 2022
Cited by 6 | Viewed by 2879
Abstract
Convection-enhanced delivery (CED) has been introduced as a concept in cancer treatment to generate high local concentrations of anticancer therapeutics and overcome the limited diffusional distribution, e.g., in the brain. RNA interference provides interesting therapeutic options to fight cancer cells but requires nanoparticulate [...] Read more.
Convection-enhanced delivery (CED) has been introduced as a concept in cancer treatment to generate high local concentrations of anticancer therapeutics and overcome the limited diffusional distribution, e.g., in the brain. RNA interference provides interesting therapeutic options to fight cancer cells but requires nanoparticulate (NP) carriers with a size below 100 nm as well as a low zeta potential for CED application. In this study, we investigated calcium phosphate NPs (CaP-NPs) as siRNA carriers for CED application. Since CaP-NPs tend to aggregate, we introduced a new terpolymer (o14PEGMA(1:1:2.5) NH3) for stabilization of CaP-NPs intended for delivery of siRNA to brain cancer cells. This small terpolymer provides PEG chains for steric stabilization, and a fat alcohol to improve interfacial activity, as well as maleic anhydrides that allow for both labeling and high affinity to Ca(II) in the hydrolyzed state. In a systematic approach, we varied the Ca/P ratio as well as the terpolymer concentration and successfully stabilized NPs with the desired properties. Labeling of the terpolymer with the fluorescent dye Cy5 revealed the terpolymer’s high affinity to CaP. Importantly, we also determined a high efficiency of siRNA binding to the NPs that caused very effective survivin siRNA silencing in F98 rat brain cancer cells. Cytotoxicity investigations with a standard cell line resulted in minor and transient effects; no adverse effects were observed in organotypic brain slice cultures. However, more specific cytotoxicity investigations are required. This study provides a systematic and mechanistic analysis characterizing the effects of the first oligomer of a new class of stabilizers for siRNA-loaded CaP-NPs. Full article
(This article belongs to the Special Issue Non-viral Gene Delivery Systems, 2nd Edition)
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16 pages, 1420 KiB  
Article
Modulation of Colorectal Tumor Behavior via lncRNA TP53TG1-Lipidic Nanosystem
by Farimah Masoumi, Sofia M. Saraiva, Belén L. Bouzo, Rafael López-López, Manel Esteller, Ángel Díaz-Lagares and María de la Fuente
Pharmaceutics 2021, 13(9), 1507; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091507 - 18 Sep 2021
Cited by 4 | Viewed by 3035
Abstract
Long non-coding RNAs (lncRNAs) are an emerging group of RNAs with a crucial role in cancer pathogenesis. In gastrointestinal cancers, TP53 target 1 (TP53TG1) is an epigenetically regulated lncRNA that represents a promising therapeutic target due to its tumor suppressor properties regulating the [...] Read more.
Long non-coding RNAs (lncRNAs) are an emerging group of RNAs with a crucial role in cancer pathogenesis. In gastrointestinal cancers, TP53 target 1 (TP53TG1) is an epigenetically regulated lncRNA that represents a promising therapeutic target due to its tumor suppressor properties regulating the p53-mediated DNA damage and the intracellular localization of the oncogenic YBX1 protein. However, to translate this finding into the clinic as a gene therapy, it is important to develop effective carriers able to deliver exogenous lncRNAs to the targeted cancer cells. Here, we propose the use of biocompatible sphingomyelin nanosystems comprising DOTAP (DSNs) to carry and deliver a plasmid vector encoding for TP53TG1 (pc(TP53TG1)-DSNs) to a colorectal cancer cell line (HCT-116). DSNs presented a high association capacity and convenient physicochemical properties. In addition, pc(TP53TG1)-DSNs showed anti-tumor activities in vitro, specifically a decrease in the proliferation rate, a diminished colony-forming capacity, and hampered migration and invasiveness of the treated cancer cells. Consequently, the proposed strategy displays a high potential as a therapeutic approach for colorectal cancer. Full article
(This article belongs to the Special Issue Non-viral Gene Delivery Systems, 2nd Edition)
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Review

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28 pages, 2738 KiB  
Review
Targeted Nanocarrier Delivery of RNA Therapeutics to Control HIV Infection
by Esinam E. Agbosu, Scott Ledger, Anthony D. Kelleher, Jing Wen and Chantelle L. Ahlenstiel
Pharmaceutics 2022, 14(7), 1352; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14071352 - 26 Jun 2022
Cited by 2 | Viewed by 2428
Abstract
Our understanding of HIV infection has greatly advanced since the discovery of the virus in 1983. Treatment options have improved the quality of life of people living with HIV/AIDS, turning it from a fatal disease into a chronic, manageable infection. Despite all this [...] Read more.
Our understanding of HIV infection has greatly advanced since the discovery of the virus in 1983. Treatment options have improved the quality of life of people living with HIV/AIDS, turning it from a fatal disease into a chronic, manageable infection. Despite all this progress, a cure remains elusive. A major barrier to attaining an HIV cure is the presence of the latent viral reservoir, which is established early in infection and persists for the lifetime of the host, even during prolonged anti-viral therapy. Different cure strategies are currently being explored to eliminate or suppress this reservoir. Several studies have shown that a functional cure may be achieved by preventing infection and also inhibiting reactivation of the virus from the latent reservoir. Here, we briefly describe the main HIV cure strategies, focussing on the use of RNA therapeutics, including small interfering RNA (siRNA) to maintain HIV permanently in a state of super latency, and CRISPR gRNA to excise the latent reservoir. A challenge with progressing RNA therapeutics to the clinic is achieving effective delivery into the host cell. This review covers recent nanotechnological strategies for siRNA delivery using liposomes, N-acetylgalactosamine conjugation, inorganic nanoparticles and polymer-based nanocapsules. We further discuss the opportunities and challenges of those strategies for HIV treatment. Full article
(This article belongs to the Special Issue Non-viral Gene Delivery Systems, 2nd Edition)
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22 pages, 3767 KiB  
Review
Treating Pulmonary Fibrosis with Non-Viral Gene Therapy: From Bench to Bedside
by Teng Huang, Jia Gao, Long Cai, Hao Xie, Yuhan Wang, Yi Wang and Qing Zhou
Pharmaceutics 2022, 14(4), 813; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14040813 - 07 Apr 2022
Cited by 4 | Viewed by 3009
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by irreversible lung scarring, which achieves almost 80% five-year mortality rate. Undeniably, commercially available pharmaceuticals, such as pirfenidone and nintedanib, exhibit certain effects on improving the well-being of IPF patients, but the [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by irreversible lung scarring, which achieves almost 80% five-year mortality rate. Undeniably, commercially available pharmaceuticals, such as pirfenidone and nintedanib, exhibit certain effects on improving the well-being of IPF patients, but the stubbornly high mortality still indicates a great urgency of developing superior therapeutics against this devastating disease. As an emerging strategy, gene therapy brings hope for the treatment of IPF by precisely regulating the expression of specific genes. However, traditional administration approaches based on viruses severely restrict the clinical application of gene therapy. Nowadays, non-viral vectors are raised as potential strategies for in vivo gene delivery, attributed to their low immunogenicity and excellent biocompatibility. Herein, we highlight a variety of non-viral vectors, such as liposomes, polymers, and proteins/peptides, which are employed in the treatment of IPF. By respectively clarifying the strengths and weaknesses of the above candidates, we would like to summarize the requisite features of vectors for PF gene therapy and provide novel perspectives on design-decisions of the subsequent vectors, hoping to accelerate the bench-to-bedside pace of non-viral gene therapy for IPF in clinical setting. Full article
(This article belongs to the Special Issue Non-viral Gene Delivery Systems, 2nd Edition)
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19 pages, 2069 KiB  
Review
Clinical Advances of siRNA-Based Nanotherapeutics for Cancer Treatment
by Dima Hattab, Amirah Mohd Gazzali and Athirah Bakhtiar
Pharmaceutics 2021, 13(7), 1009; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13071009 - 02 Jul 2021
Cited by 52 | Viewed by 4927
Abstract
Cancer is associated with single or multiple gene defects. Recently, much research has focused on incorporating genetic materials as one of the means to treat various types of carcinomas. RNA interference (RNAi) conveys an alternative genetic approach for cancer patients, especially when conventional [...] Read more.
Cancer is associated with single or multiple gene defects. Recently, much research has focused on incorporating genetic materials as one of the means to treat various types of carcinomas. RNA interference (RNAi) conveys an alternative genetic approach for cancer patients, especially when conventional medications fail. RNAi involves the inhibition of expression of specific messenger RNA that signals for uncontrollable cell growth and proliferation, most notably with carcinoma cells. This molecular technology is promising as genetic materials allow us to overcome issues associated with chemotherapeutic agents including organ damage associated with severe drug toxicities. Nonetheless, vast challenges impede successful gene therapy application, including low tumor localization, low stability and rapid clearance from the blood circulation. Owing to the limited treatment opportunities for the management of cancer, the development of effective siRNA carrier systems involving nanotherapeutics has been extensively explored. Over the past years, several siRNA nanotherapeutics have undergone a period of clinical investigation, with some demonstrating promising antitumor activities and safety profiles. Extensive observation of siRNA-nanoparticles is necessary to ensure commercial success. Therefore, this review mainly focuses on the progress of siRNAs-loaded nanoparticles that have undergone clinical trials for cancer treatment. The status of the siRNA nanotherapeutics is discussed, allowing comprehensive understanding of their gene-mediated therapeutics. Full article
(This article belongs to the Special Issue Non-viral Gene Delivery Systems, 2nd Edition)
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