Next-Generation for mRNA Vaccine Delivery

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

Deadline for manuscript submissions: 20 September 2026 | Viewed by 716

Special Issue Editor


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Guest Editor
CCRC Hauner - Comprehensive Childhood Research Centre, Ludwig Maximilians University Munich, Lindwurmstr. 4, 80337 Munich, Germany
Interests: gene therapy; modification of mRNA; targeted transfer of mRNA; translational capacity of mRNA; immunogenicity of mRNA

Special Issue Information

Dear Colleagues,

Messenger RNA (mRNA)-based therapeutics have rapidly transformed the biomedical landscape, enabling breakthroughs in vaccines, protein replacement therapies, cancer immunotherapy, and gene editing. Despite this progress, the safe, efficient, and tissue-specific delivery of mRNA remains a central challenge limiting the full therapeutic potential of these technologies. This Special Issue entitled “Next generation for mRNA vaccine delivery”, brings together cutting-edge research and perspectives that address these challenges through innovative delivery strategies and enabling technologies.

The issue highlights advances beyond first-generation lipid nanoparticles, including novel lipid architectures, polymeric and hybrid nanocarriers, biomimetic and cell-derived systems, virus-inspired platforms, and extracellular vesicle-based delivery approaches. Contributions explore strategies to improve stability, endosomal escape, targeting specificity, immune modulation, and scalability, while minimizing toxicity and off-target effects. Emphasis is also placed on delivery solutions for topical administration, e.g., oral, intranasal, and intratracheal application, as well as for systemic administration and non-injectable administration routes.

In addition, the Special Issue covers emerging concepts such as stimulus-responsive materials, programmable and modular delivery systems, and the integration of artificial intelligence and high-throughput screening for rational carrier design. Regulatory considerations, manufacturing challenges, and translational pathways are discussed to bridge the gap between laboratory innovation and clinical application.

By presenting interdisciplinary insights from materials science, nanotechnology, molecular biology, and clinical research, this Special Issue aims to define the next generation of mRNA delivery platforms and accelerate the development of safe, effective, and versatile mRNA-based therapeutics for a wide range of diseases.

Prof. Dr. Joseph Rosenecker
Guest Editor

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Keywords

  • gene therapy
  • modification of mRNA
  • targeted transfer of mRNA
  • translational capacity of mRNA
  • immunogenicity of mRNA

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Published Papers (1 paper)

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Research

30 pages, 4465 KB  
Article
Unraveling the Potential of Giardia Extracellular Vesicles as a Vaccine Candidate
by Clarissa Faria, Sandra Jesus, Bárbara Ferreira, Ágata Lourenço, Ana Isabel Sebastião, Daniela Mateus, Bruno M. Neves, Olga Borges, Maria Teresa Cruz and Maria do Céu Sousa
Pharmaceutics 2026, 18(4), 461; https://doi.org/10.3390/pharmaceutics18040461 - 9 Apr 2026
Viewed by 481
Abstract
Objectives: This study aimed to investigated the role of Giardia extracellular vesicles (EVs) in intercellular communication and to evaluated their potential as vaccine candidates. Methods: The immunomodulatory effects of Giardia EVs were assessed in mouse macrophages and human monocyte-derived dendritic cells (Mo-DCs), [...] Read more.
Objectives: This study aimed to investigated the role of Giardia extracellular vesicles (EVs) in intercellular communication and to evaluated their potential as vaccine candidates. Methods: The immunomodulatory effects of Giardia EVs were assessed in mouse macrophages and human monocyte-derived dendritic cells (Mo-DCs), with a particular focus on key inflammatory signaling pathways. In vivo immunogenicity was evaluated following EV administration, and the antigenic composition of EV cargo was characterized by proteomic analysis. Results: Giardia EVs activated pro-inflammatory signaling pathways in mouse macrphages, including SAPK/JNK, ERK1/2, and NF-κB. This activation was associated with IκB-α degradation and nuclear translocation of p65. Furthermore, EV stimulation significantly upregulated the expression of pro-inflammatory genes, including Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf, with log2 fold changes ranging from 3.9 to 15.8. Consistently, EVs increased iNOS protein expression (28–45%) and nitrite production (9.6–12.3-fold). In human Mo-DCs, Giardia EVs promoted cellular maturation, as evidenced by increased expression of MHC-II, CD80, and CD86, and enhanced T-cell proliferation with a Th1-skewed profile. In vivo immunization induced antigen-specific antibody responses, with IgG subclass distribution indicative of a balanced Th1/Th2 response. Proteomic analysis identified immunoreactive EV-associated proteins, including elongation factor 1-alpha, α-7.3 giardin, tubulin, and variant surface proteins (VSPs), which are well-established antigens in Giardia infection, with prominent bands observed at approximately 22 kDa and 50 kDa. Conclusions: Collectively, these findings demonstrate that Giardia EVs modulate innate immune responses in vitro, elicit antigen-specific humoral immunity in vivo, and contain conserved immunogenic proteins. These properties support their potential as a promising cell-free vaccine platform against giardiasis. Full article
(This article belongs to the Special Issue Next-Generation for mRNA Vaccine Delivery)
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