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Review
. 2025 May 4;17(5):609.
doi: 10.3390/pharmaceutics17050609.

Immune Modulation with Oral DNA/RNA Nanoparticles

Ulpan Kart  1 , Aigul Raimbekova  1 , Sergey Yegorov  1 , Gonzalo Hortelano  1
Affiliations
Review

Immune Modulation with Oral DNA/RNA Nanoparticles

Ulpan Kart et al. Pharmaceutics. .

Abstract

The oral delivery of DNA/RNA nanoparticles represents a transformative approach in immunotherapy and vaccine development. These nanoparticles enable targeted immune modulation by delivering genetic material to specific cells in the gut-associated immune system, triggering both mucosal and systemic immune responses. Unlike parenteral administration, the oral route offers a unique immunological environment that supports both tolerance and activation, depending on the formulation design. This review explores the underlying mechanisms of immune modulation by DNA/RNA nanoparticles, their design and delivery strategies, and recent advances in their application. Emphasis is placed on strategies to overcome physiological barriers such as acidic pH, enzymatic degradation, mucus entrapment, and epithelial tight junctions. Special attention is given to the role of gut-associated lymphoid tissue in mediating immune responses and the therapeutic potential of these systems in oral vaccine platforms, food allergies, autoimmune diseases, and chronic inflammation. Despite challenges, recent advances in nanoparticle formulation support the translation of these technologies into clinical applications for both therapeutic immunomodulation and vaccination.

Keywords: DNA; LNP; RNA; chitosan; drug delivery; immune response; nanoparticles.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 3
Figure 3
Mechanisms of oral tolerance prevent inflammatory responses to ingested antigens by promoting immune regulation in the gut. Peyer’s patches and mesenteric lymph nodes (mLNs) facilitate antigen uptake, where DCs present them to T cells, inducing Tregs. These Tregs produce TGF-β and IL-10, suppressing inflammation and maintaining gut homeostasis [139,140].
Figure 1
Figure 1
Advantages of various types of nanoparticles in the context of oral delivery.
Figure 2
Figure 2
Biological barriers affecting the oral delivery of DNA/RNA nanoparticles.
See this image and copyright information in PMC

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