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Advances in Therapeutic RNA Design and Delivery
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Advances in Therapeutic RNA Design and Delivery

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

Deadline for manuscript submissions: closed (1 March 2022) | Viewed by 24341

Special Issue Editor

Dr. Carla Lucia Esposito

E-Mail Website
Guest Editor
Istituto per l’Endocrinologia e l’Oncologia Sperimentale del CNR ‘‘G. Salvatore’’, Via S. Pansini 5, 80131 Naples, Italy
Interests: aptamers; cancer; targeted delivery; SELEX
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nucleic acid therapeutics, including small interfering RNAs (siRNAs), microRNAs (miRs)/antimiRs, and CRISP guide RNAs (gRNAs), are emerging as safe and highly promising molecules for the precise treatment of refractory aggressive diseases. However, the development of RNA-based therapeutics still presents important challenges. Indeed, RNAs are prone to degradation, are potentially immunogenic, and require a delivery vehicle to overcome barriers in the organism and specifically accumulate in the target cells. Several groups have addressed these hurdles in the last decade. Enhancements of the in vivo stability of synthetic oligonucleotides have been achieved using different chemical modifications. Further, many synthetic delivery carriers have been proposed to improve RNA-based drug safety and efficacy and reduce off-target effects. This Special Issue will address diverse areas related to the molecular design and targeted delivery approaches of therapeutic RNAs. It will highlight advances in RNA-based therapy formulation, safety, stability, and efficacy.

Dr. Carla Lucia Esposito
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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

  • therapeutic oliconucleotides
  • siRNA
  • miRNA
  • delivery systems
  • RNA chemistry
  • targeted therapy
  • aptamers

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Published Papers (3 papers)

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Review

14 pages, 7428 KiB  
Review
Recent Advances in the Development of Exogenous dsRNA for the Induction of RNA Interference in Cancer Therapy
by Tatiana S. Golubeva, Viktoria A. Cherenko and Konstantin E. Orishchenko
Molecules 2021, 26(3), 701; https://doi.org/10.3390/molecules26030701 - 29 Jan 2021
Cited by 1 | Viewed by 5716
Abstract
Selective regulation of gene expression by means of RNA interference has revolutionized molecular biology. This approach is not only used in fundamental studies on the roles of particular genes in the functioning of various organisms, but also possesses practical applications. A variety of [...] Read more.
Selective regulation of gene expression by means of RNA interference has revolutionized molecular biology. This approach is not only used in fundamental studies on the roles of particular genes in the functioning of various organisms, but also possesses practical applications. A variety of methods are being developed based on gene silencing using dsRNA—for protecting agricultural plants from various pathogens, controlling insect reproduction, and therapeutic techniques related to the oncological disease treatment. One of the main problems in this research area is the successful delivery of exogenous dsRNA into cells, as this can be greatly affected by the localization or origin of tumor. This overview is dedicated to describing the latest advances in the development of various transport agents for the delivery of dsRNA fragments for gene silencing, with an emphasis on cancer treatment. Full article
(This article belongs to the Special Issue Advances in Therapeutic RNA Design and Delivery)
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19 pages, 1270 KiB  
Review
Aptamer-Based In Vivo Therapeutic Targeting of Glioblastoma
by Valeriana Cesarini, Chiara Scopa, Domenico Alessandro Silvestris, Andrea Scafidi, Valerio Petrera, Giada Del Baldo and Angela Gallo
Molecules 2020, 25(18), 4267; https://doi.org/10.3390/molecules25184267 - 17 Sep 2020
Cited by 19 | Viewed by 4758
Abstract
Glioblastoma (GBM) is the most aggressive, infiltrative, and lethal brain tumor in humans. Despite the extensive advancement in the knowledge about tumor progression and treatment over the last few years, the prognosis of GBM is still very poor due to the difficulty of [...] Read more.
Glioblastoma (GBM) is the most aggressive, infiltrative, and lethal brain tumor in humans. Despite the extensive advancement in the knowledge about tumor progression and treatment over the last few years, the prognosis of GBM is still very poor due to the difficulty of targeting drugs or anticancer molecules to GBM cells. The major challenge in improving GBM treatment implicates the development of a targeted drug delivery system, capable of crossing the blood–brain barrier (BBB) and specifically targeting GBM cells. Aptamers possess many characteristics that make them ideal novel therapeutic agents for the treatment of GBM. They are short single-stranded nucleic acids (RNA or ssDNA) able to bind to a molecular target with high affinity and specificity. Several GBM-targeting aptamers have been developed for imaging, tumor cell isolation from biopsies, and drug/anticancer molecule delivery to the tumor cells. Due to their properties (low immunogenicity, long stability, and toxicity), a large number of aptamers have been selected against GBM biomarkers and tested in GBM cell lines, while only a few of them have also been tested in in vivo models of GBM. Herein, we specifically focus on aptamers tested in GBM in vivo models that can be considered as new diagnostic and/or therapeutic tools for GBM patients’ treatment. Full article
(This article belongs to the Special Issue Advances in Therapeutic RNA Design and Delivery)
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18 pages, 900 KiB  
Review
Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy
by Francesco Mainini and Michael R. Eccles
Molecules 2020, 25(11), 2692; https://doi.org/10.3390/molecules25112692 - 10 Jun 2020
Cited by 122 | Viewed by 12692
Abstract
RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor [...] Read more.
RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient’s therapeutic response. Full article
(This article belongs to the Special Issue Advances in Therapeutic RNA Design and Delivery)
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