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RNA Vaccines and Therapeutics: Challenges and Opportunities
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RNA Vaccines and Therapeutics: Challenges and Opportunities

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 5686

Special Issue Editor

Prof. Dr. Seong-Wook Lee

E-Mail Website
Guest Editor
Department of Bioconvergence Engineering, Research Institute of Advanced Omics, Dankook University, Yongin 16890, Republic of Korea
Interests: RNA-based therapeutics and diagnostics; gene therapy; cancer; genetic disease; immune disorder; virus, microRNAs; ribozyme; aptamer; genome editing

Special Issue Information

Dear Colleagues,

Advances in RNA-based technologies such as RNA interference and RNA/genome editing have initiated a new era in the field of therapeutics, with potential to overcome the limitation of existing treatments through their features, including the specificity, efficacy, flexibility and targetability of non-druggable targets, etc. Moreover, the success of messenger RNA as a vaccine against SARS-CoV-2 has further spurred and expanded medical uses of RNA. This Special Issue aims to provide an overview of the current status and future trends of the cutting-edge RNA-based technologies in the medical field. We welcome contributions, including original articles, reviews and perspectives, on RNA-based therapeutics and vaccinology, from basic research to clinical applications.

Prof. Dr. Seong-Wook Lee
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • RNA-based therapy
  • RNA vaccine
  • mRNA
  • circRNA
  • saRNA
  • non-coding RNA/sRNA
  • microRNA/siRNA/antisense RNA
  • RNA aptamer
  • ribozyme
  • RNA editing/genome editing

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Published Papers (3 papers)

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Research

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13 pages, 2000 KiB  
Article
Design and Expression of Fasciola hepatica Multiepitope Constructs Using mRNA Vaccine Technology
by Javier Sánchez-Montejo, Tania Strilets, Raúl Manzano-Román, Julio López-Abán, Mariano A. García-Blanco, Belén Vicente and Antonio Muro
Int. J. Mol. Sci. 2025, 26(3), 1190; https://doi.org/10.3390/ijms26031190 - 30 Jan 2025
Viewed by 725
Abstract
Fasciola hepatica is a parasitic trematode responsible for fascioliasis, a significant zoonotic disease affecting livestock worldwide, as well as humans. This study identifies peptides with potential for use in vaccines against Fasciola hepatica and validates multi-epitope constructs from those peptides in vitro. Putative [...] Read more.
Fasciola hepatica is a parasitic trematode responsible for fascioliasis, a significant zoonotic disease affecting livestock worldwide, as well as humans. This study identifies peptides with potential for use in vaccines against Fasciola hepatica and validates multi-epitope constructs from those peptides in vitro. Putative protein sequences derived from the genome of F. hepatica were integrated with phase-specific transcriptomic data to prioritize highly expressed proteins. Among these, extracellular proteins were selected using DeepLoc 2.0 and strong binding affinities across diverse human and murine alleles were predicted with the IEDB MHC II tool. Peptides were further selected based on their toxicity, immunogenicity, and allergenicity. Finally, 55 high-priority candidates were obtained. To express these candidates, mRNA constructs encoding various combinations of these peptides were designed, synthesized using in vitro transcription with T7 or SP6 RNA polymerases, and transfected into cells for expression analysis. SP6 polymerase produced proper capping using CleanCapAG and was far superior in transcribing peptide constructs. Peptides fused in frame with eGFP were expressed efficiently, particularly when peptides were positioned at the 3′ terminus, opening a new field of peptide vaccines created using mRNA technology. Full article
(This article belongs to the Special Issue RNA Vaccines and Therapeutics: Challenges and Opportunities)
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Review

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11 pages, 1614 KiB  
Review
In Vitro Self-Circularization Methods Based on Self-Splicing Ribozyme
by Kyung Hyun Lee, Nan-Ee Lee and Seong-Wook Lee
Int. J. Mol. Sci. 2024, 25(17), 9437; https://doi.org/10.3390/ijms25179437 - 30 Aug 2024
Viewed by 2310
Abstract
In vitro circular RNA (circRNA) preparation methods have been gaining a lot of attention recently as several reports suggest that circRNAs are more stable, with better performances in cells and in vivo, than linear RNAs in various biomedical applications. Self-splicing ribozymes are considered [...] Read more.
In vitro circular RNA (circRNA) preparation methods have been gaining a lot of attention recently as several reports suggest that circRNAs are more stable, with better performances in cells and in vivo, than linear RNAs in various biomedical applications. Self-splicing ribozymes are considered a major in vitro circRNA generation method for biomedical applications due to their simplicity and efficiency in the circularization of the gene of interest. This review summarizes, updates, and discusses the recently developed self-circularization methods based on the self-splicing ribozyme, such as group I and II intron ribozymes, and the pros and cons of each method in preparing circRNA in vitro. Full article
(This article belongs to the Special Issue RNA Vaccines and Therapeutics: Challenges and Opportunities)
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25 pages, 12170 KiB  
Review
Nucleic Acid Armor: Fortifying RNA Therapeutics through Delivery and Targeting Innovations for Immunotherapy
by Yi Jiang, Bolong Jiang, Zhenru Wang, Yuxi Li, James Chung Wai Cheung, Bohan Yin and Siu Hong Dexter Wong
Int. J. Mol. Sci. 2024, 25(16), 8888; https://doi.org/10.3390/ijms25168888 - 15 Aug 2024
Cited by 5 | Viewed by 2136
Abstract
RNA is a promising nucleic acid-based biomolecule for various treatments because of its high efficacy, low toxicity, and the tremendous availability of targeting sequences. Nevertheless, RNA shows instability and has a short half-life in physiological environments such as the bloodstream in the presence [...] Read more.
RNA is a promising nucleic acid-based biomolecule for various treatments because of its high efficacy, low toxicity, and the tremendous availability of targeting sequences. Nevertheless, RNA shows instability and has a short half-life in physiological environments such as the bloodstream in the presence of RNAase. Therefore, developing reliable delivery strategies is important for targeting disease sites and maximizing the therapeutic effect of RNA drugs, particularly in the field of immunotherapy. In this mini-review, we highlight two major approaches: (1) delivery vehicles and (2) chemical modifications. Recent advances in delivery vehicles employ nanotechnologies such as lipid-based nanoparticles, viral vectors, and inorganic nanocarriers to precisely target specific cell types to facilitate RNA cellular entry. On the other hand, chemical modification utilizes the alteration of RNA structures via the addition of covalent bonds such as N-acetylgalactosamine or antibodies (antibody–oligonucleotide conjugates) to target specific receptors of cells. The pros and cons of these technologies are enlisted in this review. We aim to review nucleic acid drugs, their delivery systems, targeting strategies, and related chemical modifications. Finally, we express our perspective on the potential combination of RNA-based click chemistry with adoptive cell therapy (e.g., B cells or T cells) to address the issues of short duration and short half-life associated with antibody–oligonucleotide conjugate drugs. Full article
(This article belongs to the Special Issue RNA Vaccines and Therapeutics: Challenges and Opportunities)
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