Off the beaten path: Novel mRNA-nanoformulations for therapeutic vaccination against HIV

Do COVID-19 RNA-based vaccines put at risk of immune-mediated diseases? In reply to “potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases”

“…Modifications in nucleoside and nanoparticle composition through a proper manufacturing may help to prevent some of these drawbacks. For instance, the substitution of uridine with pseudouridine was shown to reduce immunogenicity and type I IFN production while enhancing the synthesis of viral antigenic proteins [ 10 ]. A strong type I IFN response may, in fact, negatively affect the vaccine efficacy by suppressing the process of mRNA translation [ 10 ].…”

“…For instance, the substitution of uridine with pseudouridine was shown to reduce immunogenicity and type I IFN production while enhancing the synthesis of viral antigenic proteins [ 10 ]. A strong type I IFN response may, in fact, negatively affect the vaccine efficacy by suppressing the process of mRNA translation [ 10 ]. However, type I IFNs play a beneficial role in strengthening the antiviral response, as they favor the maturation of DCs, the CD8+ T cell-mediated cytotoxicity and the secretion of several cytokines, like interleukin (IL)-12 and IL-23 [ 11 ].…”

“…Notably, polymorphisms in the genes encoding these cytokines or their receptors have been associated with the susceptibility to autoimmune diseases [ 12 ]. Additionally, an excessive production of type I IFNs may result in the breakdown of the immunological tolerance and, therefore, in autoimmunity [ 10 ].…”

HIV mRNA Vaccines—Progress and Future Paths

“…Later, it was found that even direct injection of naked mRNA into mouse skeletal muscle results in protein translation and expression [ 107 , 108 ]. However, using mRNA for therapeutic or vaccine purposes was not feasible because of the instability of RNA molecules, a lack of efficient delivery methods, uncontrollable activation of innate immunity through RNA sensors and difficulties in large-scale manufacturing of mRNA [ 107 , 109 ]. In recent years, technological advances and improved delivery methods have addressed these obstacles and mRNA-based vaccines have emerged as a promising new platform to deliver antigens.…”

Layer-by-Layer technique as a versatile tool for gene delivery applications

“…Several studies were performed for optimizing the delivery of siRNA to specific tissue and organ systems in vivo [96,97]. Delivery of siRNA in vivo using the polymers system was carried out to Ewing Sarcoma (soft tissue sarcoma) [98], brain [99], melanoma (skin cancer) [100], and macrophages modification [101]. LbL assembly demonstrates the highest efficiency and stability for the transfer of functional siRNA molecules, which is highly relevant considering their potential clinical application.…”