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Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier
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From RNA to DNA: How Cargo Identity Reprograms Lipid Nanoparticle Architecture and Function
Erica Quagliarini1,2, Daniela Pozzi1,2, Giulio Caracciolo1,2
1NanoDelivery Lab, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Advanced Healthcare Materials
|February 3, 2026
Summary
DNA-loaded lipid nanoparticles (LNPs) present unique challenges compared to RNA-LNPs due to DNA
Area of Science:
- Nanomedicine
- Gene Therapy
- Biotechnology
Background:
- Lipid nanoparticles (LNPs) are a leading platform for genetic material delivery, exemplified by mRNA COVID-19 vaccines.
- While RNA-LNPs are clinically mature, DNA-loaded LNPs are less explored despite therapeutic potential for gene replacement and editing.
Purpose of the Study:
- To review and analyze the distinct characteristics of DNA-loaded LNPs.
- To compare DNA-LNPs with RNA-LNPs and earlier lipoplexes.
- To identify design strategies and challenges for DNA-LNP development.
Main Methods:
- Literature review focusing on structural, compositional, and biological differences between DNA-LNPs and RNA-LNPs.
- Analysis of DNA's influence on particle formation, biomolecular corona, and biological behavior.
- Examination of specific design considerations for DNA-LNPs.
Main Results:
- DNA-LNPs are typically larger, more heterogeneous, and multilamellar than RNA-LNPs due to DNA's properties.
- DNA significantly alters the biomolecular corona, impacting immune response, circulation, and targeting.
- Specific design strategies like cationic lipids and optimized PEGylation are needed for DNA-LNPs.
Conclusions:
- DNA-LNPs require distinct formulation approaches, differing from RNA-LNP strategies.
- A cargo-informed design is crucial for realizing the therapeutic potential of DNA-LNPs.
- Further research is needed to overcome the unique challenges associated with DNA-LNP development.
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