Special Issue "Multi-Component Delivery Systems for Targeted Delivery of Nucleic Acids"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: 18 November 2020.

Special Issue Editor

Dr. Hamidreza Montazeri Aliabadi
Website
Guest Editor
Chapman University, Orange, United States
Interests: targeted delivery systems; siRNA; breast cancer; signaling pathways; innate and acquired resistance; CRISPR

Special Issue Information

Dear Colleagues,

Approaches to RNA interference have made a significant impact on research strategies and methodologies since the turn of the century. These approaches include but are not limited to plasmid DNA, small interfering RNA (siRNA), short hairpin RNA (shRNA), micro RNA (miRNA), oligonucleotides, and most recently, clustered regularly interspaced short palindromic repeats (CRISPR). Each approach offers certain advantages, and of course, has its own flaws. These approaches have provided reliable tools in basic and translational research, with the ability to target virtually any protein in a variety of mammalian cells and “silence” the expression of the target for a short period of time or permanently. However, despite promising initial results, this significant impact has not been translated into the wide clinical applications for which we all have hoped. Nucleic acid delivery is difficult, and has proven to be even more challenging in vivo. We have not given up yet. We are still exploring new approaches and novel carriers on a regular basis. This Special Issue aims to include review and research papers that provide a comprehensive look at the most recent attempts in nucleic acid delivery, focusing on multi-component delivery systems designed as safe and effective carriers. It is also hoped to shine light on the future directions for nucleic acid delivery.

Dr. Hamidreza Montazeri Aliabadi
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. Pharmaceuticals 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 1400 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

  • targeted delivery
  • multicomponent
  • RNA interference
  • in vitro
  • in vivo
  • shRNA
  • miRNA
  • oligonucleotides
  • CRISPR
  • plasmid

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Published Papers (2 papers)

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Research

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Open AccessArticle
Characterization of iRGD-Ligand Modified Arginine-Histidine-Rich Peptides for Nucleic Acid Therapeutics Delivery to αvβ3 Integrin-Expressing Cancer Cells
Pharmaceuticals 2020, 13(10), 300; https://doi.org/10.3390/ph13100300 - 10 Oct 2020
Abstract
Efficient and specific delivery of nucleic acid (NA) therapeutics to tumor cells is extremely important for cancer gene therapy. Various therapeutic strategies include delivery of DNA-therapeutics such as immunostimulatory or suicide genes and delivery of siRNA-therapeutics able to silence expression of cancer-related genes. [...] Read more.
Efficient and specific delivery of nucleic acid (NA) therapeutics to tumor cells is extremely important for cancer gene therapy. Various therapeutic strategies include delivery of DNA-therapeutics such as immunostimulatory or suicide genes and delivery of siRNA-therapeutics able to silence expression of cancer-related genes. Peptides are a promising class of non-viral vehicles which are biodegradable and can efficiently condense, protect and specifically deliver NA to the cells. Here we designed arginine-histidine-rich peptide carriers consisting of an iRGD ligand to target αvβ3 integrins and studied them as vehicles for DNA and siRNA delivery to cancer cells. Combination of iRGD-modified and unmodified arginine–histidine-rich peptides during NA complexation resulted in carriers with different ligand contents. The NA-binding and protecting properties in vitro transfection efficiency and cytotoxicity of the DNA- and siRNA-polyplexes were studied and the most efficient carrier RGD1 was determined. The ability of the peptides to mediate specific intracellular uptake was confirmed inhuman cervical carcinoma (HeLa), human kidney (293T) and human pancreatic (PANC-1) cell lines with different αvβ3 integrins surface expression. By means of RGD1 carrier, efficient delivery of the herpes simplex virus (HSV-1) thymidine kinase gene to PANC-1 cells was demonstrated. Subsequent ganciclovir treatment led to a reduction of PANC-1 cells’ viability by up to 54%. Efficient RNAi-mediated down-regulation of GFP and VEGFA gene expression was achieved in MDA-MB-231-GFP+ breast cancer and EA.hy926 endothelial cells, respectively, by means of RGD1/siRNA polyplexes. Here we demonstrated that the peptide carrier RGD1 can be considered as promising candidate for development of NA therapeutics delivery systems useful in cancer gene therapy. Full article
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Review

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Open AccessReview
Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside
Pharmaceuticals 2020, 13(10), 294; https://doi.org/10.3390/ph13100294 - 07 Oct 2020
Abstract
The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, [...] Read more.
The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described the intracellular barriers such as endosomal trap and off-target effects of siRNAs. Moreover, we have reported most of the strategies and techniques in overcoming these barriers, followed by critical comments in translating these molecules from bench to bedside. Full article
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