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Special Issue "Gene Delivery"

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

Deadline for manuscript submissions: 31 December 2018

Special Issue Editor

Guest Editor
Prof. Dr. T.J. Thomas

Department of Medicine, Rutgers Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA
Website | E-Mail
Interests: Breast Cancer; Polyamines; Nanotechnology; Gene Delivery; Oligonucleotides; Estrogen Receptor; Antiestrogens

Special Issue Information

Dear Colleagues,

Gene therapy promises effective treatment for a variety of diseases, including cystic fibrosis, cancer and Alzheimer’s disease. Safe and efficient gene delivery vehicles are essential to advance gene therapy to clinical arena. Several investigators are involved in developing new carrier materials and fabricating functional materials aimed at improving gene therapy protocols. This Special Issue of Molecules will publish a collection of articles with a focus on “Gene Delivery”, including DNA and RNA delivery using viral and non-viral vectors. Original articles and reviews will be published in this Special Issue.

Prof. Dr. T.J. Thomas
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 papers will be 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 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 1800 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

  • Aptamer delivery
  • Cationic polymers and gene delivery
  • Co-delivery of drugs and genes
  • Dendrimers and gene delivery
  • DNA-carrier interactions
  • DNA/RNA condensation
  • Gene delivery
  • miRNA delivery
  • Nanocarriers as gene delivery vehicles
  • Non-viral gene delivery
  • siRNA delivery
  • Stimuli sensitive delivery vehicles

Published Papers (4 papers)

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Research

Jump to: Review

Open AccessArticle DNA Interaction with Head-to-Tail Associates of Cationic Surfactants Prevents Formation of Compact Particles
Molecules 2018, 23(7), 1576; https://doi.org/10.3390/molecules23071576
Received: 30 May 2018 / Revised: 26 June 2018 / Accepted: 26 June 2018 / Published: 28 June 2018
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Abstract
Cationic azobenzene-containing surfactants are capable of condensing DNA in solution with formation of nanosized particles that can be employed in gene delivery. The ratio of surfactant/DNA concentration and solution ionic strength determines the result of DNA-surfactant interaction: Complexes with a micelle-like surfactant associates
[...] Read more.
Cationic azobenzene-containing surfactants are capable of condensing DNA in solution with formation of nanosized particles that can be employed in gene delivery. The ratio of surfactant/DNA concentration and solution ionic strength determines the result of DNA-surfactant interaction: Complexes with a micelle-like surfactant associates on DNA, which induces DNA shrinkage, DNA precipitation or DNA condensation with the emergence of nanosized particles. UV and fluorescence spectroscopy, low gradient viscometry and flow birefringence methods were employed to investigate DNA-surfactant and surfactant-surfactant interaction at different NaCl concentrations, [NaCl]. It was observed that [NaCl] (or the Debye screening radius) determines the surfactant-surfactant interaction in solutions without DNA. Monomers, micelles and non-micellar associates of azobenzene-containing surfactants with head-to-tail orientation of molecules were distinguished due to the features of their absorption spectra. The novel data enabled us to conclude that exactly the type of associates (together with the concentration of components) determines the result of DNA-surfactant interaction. Predomination of head-to-tail associates at 0.01 M < [NaCl] < 0.5 M induces DNA aggregation and in some cases DNA precipitation. High NaCl concentration (higher than 0.8 M) prevents electrostatic attraction of surfactants to DNA phosphates for complex formation. DAPI dye luminescence in solutions with DNA-surfactant complexes shows that surfactant tails overlap the DNA minor groove. The addition of di- and trivalent metal ions before and after the surfactant binding to DNA indicate that the bound surfactant molecules are located on DNA in islets. Full article
(This article belongs to the Special Issue Gene Delivery)
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Graphical abstract

Open AccessArticle Synthesis and Comparative Evaluation of Novel Cationic Amphiphile C12-Man-Q as an Efficient DNA Delivery Agent In Vitro
Molecules 2018, 23(7), 1540; https://doi.org/10.3390/molecules23071540
Received: 28 May 2018 / Revised: 15 June 2018 / Accepted: 21 June 2018 / Published: 26 June 2018
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Abstract
New amphiphilic 1,4-DHP derivative C12-Man-Q with remoted cationic moieties at positions 2 and 6 was synthesised to study DNA delivery activity. The results were compared with data obtained for cationic 1,4-DHP derivative D19, which is known to be the most efficient one
[...] Read more.
New amphiphilic 1,4-DHP derivative C12-Man-Q with remoted cationic moieties at positions 2 and 6 was synthesised to study DNA delivery activity. The results were compared with data obtained for cationic 1,4-DHP derivative D19, which is known to be the most efficient one among the previously tested 1,4-DHP amphiphiles. We analysed the effects of C12-Man-Q concentration, complexation media, and complex/cell contact time on the gene delivery effectiveness and cell viability. Transmission electron microscopy data confirms that lipoplexes formed by the compound C12-Man-Q were quite uniform, vesicular-like structures with sizes of about 50 nm, and lipoplexes produced by compound D19 were of irregular shapes, varied in size in the range of 25–80 nm. Additionally, confocal microscopy results revealed that both amphiphiles effectively delivered green fluorescent protein expression plasmid into BHK-21 cells and produced a fluorescent signal with satisfactory efficiency, although compound C12-Man-Q was more cytotoxic to the BHK-21 cells with an increase of concentration. It can be concluded that optimal conditions for C12-Man-Q lipoplexes delivery in BHK-21 cells were the serum free media without 0.15 M NaCl, at an N/P ratio of 0.9. Compound D19 showed higher transfection efficiency to transfect BHK-21 and Cos-7 cell lines, when transfecting active proliferating cells. Although D19 was not able to transfect all studied cell lines we propose that it could be cell type specific. The compound C12-Man-Q showed modest delivery activity in all used cell lines, and higher activity was obtained in the case of H2-35 and B16 cells. The transfection efficiency in cell lines MCF-7, HeLa, and Huh-7 appears to be comparable to the reference compound D19 and minimal in the HepG2 cell line. Full article
(This article belongs to the Special Issue Gene Delivery)
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Graphical abstract

Open AccessArticle Development of a Mouse Model of Prostate Cancer Using the Sleeping Beauty Transposon and Electroporation
Molecules 2018, 23(6), 1360; https://doi.org/10.3390/molecules23061360
Received: 30 March 2018 / Revised: 20 May 2018 / Accepted: 1 June 2018 / Published: 5 June 2018
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Abstract
The Sleeping Beauty (SB) transposon system is non-viral and uses insertional mutagenesis, resulting in the permanent expression of transferred genes. Although the SB transposon is a useful method for establishing a mouse tumor model, there has been difficulty in using this method to
[...] Read more.
The Sleeping Beauty (SB) transposon system is non-viral and uses insertional mutagenesis, resulting in the permanent expression of transferred genes. Although the SB transposon is a useful method for establishing a mouse tumor model, there has been difficulty in using this method to generate tumors in the prostate. In the present study, electroporation was used to enhance the transfection efficiency of the SB transposon. To generate tumors, three constructs (a c-Myc expression cassette, a HRAS (HRas proto-oncogene, GTPase) expression cassette and a shRNA against p53) contained within the SB transposon plasmids were directly injected into the prostate. Electroporation was conducted on the injection site after the injection of the DNA plasmid. Following the tumorigenesis, the tumors were monitored by animal PET imaging and identified by gross observation. After this, the tumors were characterized by using histological and immunohistochemical techniques. The expression of the targeted genes was analyzed by Real-Time qRT-PCR. All mice subjected to the injection were found to have prostate tumors, which was supported by PSA immunohistochemistry. To our knowledge, this is the first demonstration of tumor induction in the mouse prostate using the electroporation-enhanced SB transposon system in combination with c-Myc, HRAS and p53. This model serves as a valuable resource for the future development of SB-induced mouse models of cancer. Full article
(This article belongs to the Special Issue Gene Delivery)
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Review

Jump to: Research

Open AccessReview MicroRNA-Regulated Gene Delivery Systems for Research and Therapeutic Purposes
Molecules 2018, 23(7), 1500; https://doi.org/10.3390/molecules23071500
Received: 30 May 2018 / Revised: 18 June 2018 / Accepted: 20 June 2018 / Published: 21 June 2018
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Abstract
Targeted gene delivery relies on the ability to limit the expression of a transgene within a defined cell/tissue population. MicroRNAs represent a class of highly powerful and effective regulators of gene expression that act by binding to a specific sequence present in the
[...] Read more.
Targeted gene delivery relies on the ability to limit the expression of a transgene within a defined cell/tissue population. MicroRNAs represent a class of highly powerful and effective regulators of gene expression that act by binding to a specific sequence present in the corresponding messenger RNA. Involved in almost every aspect of cellular function, many miRNAs have been discovered with expression patterns specific to developmental stage, lineage, cell-type, or disease stage. Exploiting the binding sites of these miRNAs allows for construction of targeted gene delivery platforms with a diverse range of applications. Here, we summarize studies that have utilized miRNA-regulated systems to achieve targeted gene delivery for both research and therapeutic purposes. Additionally, we identify criteria that are important for the effectiveness of a particular miRNA for such applications and we also discuss factors that have to be taken into consideration when designing miRNA-regulated expression cassettes. Full article
(This article belongs to the Special Issue Gene Delivery)
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Figure 1

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Advances in mitochondria-targeted gene delivery
Author: Kwang-il Lim
Abstract: Mitochondria are the energy-producing essential organelles of cells. Mitochondrial dysfunctions indirectly link to or directly lead to various syndromes and diseases including Kearns-Sayre syndrome (KSS), Leigh syndrome (LS), Leber hereditary optic neuropathy (LHON) and Alpers disease. Mitochondrial dysfunctions mostly result from mutations of mitochondrial genomes and nuclear genes that encode mitochondrial components. However, complete correction of the mutated genetic parts in cells relevant to mitochondrial structures and functions is technically challenging. Instead, there have been diverse attempts to provide fully functional mitochondrial components with cells via intracellular delivery of corrected genetic units. In this review, we will especially focus on discussing recent novel physical, chemical and biological approaches to transfer genetic cargos into mitochondria and the following physiological changes.

Title: A tool or a toy? Human Artificial Chromosomes for gene delivery and kinetochore studies".
Author: Dr. Natalie Kouprina

Title: Gene delivery into inner ear and treatment
Author: Sho Kanzaki
Abstract: The most of sensorineural hearing loss damage to the cochlea including lost hair cells (HCs) and spiral ganglion neurons (SGNs).
Mammalian cochlear HC loss cannot regenerate. The protection from SGN from degeneration has also implications for cochlear implant to patients with severe deafness.
We review the gene delivery for treatment in animal experiments.
Transgene expression of the neurotrophic factor can maintain SGN and describe potential new therapeutic interventions.
We also summarized viral vectors and introduced the gene delivery for regeneration and protection of cochlear HCs.

Title: Gene delivery into inner ear - its clinical implication
Author: Sho Kanzaki
Abstract: Gene delivery introduction into inner ear expected the inner ear regeneration and protection of neural degenerationfor patients with sensorineural hearing loss. inner ear is surrounded by bony capsule, however, two membranes are Gene delivery with Atoh1 can regenerate sensory cells or hair cells in animals. Delivery of neurotrophic factor can also protect auditory neuron from degeneration and could improve hearing results in cochlear implant patients.

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