Engineering Lipid Self-Assembling Nanoparticles as Novel mRNA-based Vaccine Platforms

Prof. Dr. Giuseppe De Rosa1) – University of Naples Federico II

+ Show more


Professor Dr. Giuseppe De RosaDepartment of Pharmacy, University Federico II of Naples, Via Domenico Montensanto 49, 80131 Naples, Italy

People involved

Dr. Virginia Campani and Dr. Valeria Nele - Department of Pharmacy, University of Naples Federico II

Dr. Fabio Palombo - Takis S.r.l., Via di Castel Romano 100 – 00128 Rome, Italy

Dr. Paolo Maiuri - Istituto FIRC di Oncologia Molecolare (IFOM), Via Adamello 16 - 20139 Milan, Italy


Messenger RNA (mRNA)-based vaccines are attractive candidates for the development of next-generation vaccines. To overcome some of the biopharmaceutical challenges that hamper mRNA administration (e.g. its rapid degradation in biological fluids and poor uptake into the target cells), nanocarriers such as lipid nanoparticles (LNPs) have been used in the two mRNA-based vaccines approved in 2021.1)2) To preserve their in vivo efficacy, mRNA-loaded LNP vaccines need to be stored and transported at extremely low temperatures, which limits their widespread use. Alternative formulations for mRNA-based vaccines with long shelf life at refrigerated temperatures are needed.

Here, we aim to overcome these issues by leveraging the lipid self-assembling nanoparticle (SANP) technology for the development of mRNA-based vaccines. Lipid SANP formulations have shown remarkable biocompatibility, high RNA encapsulation efficiency, and enhanced intracellular release.3) Furthermore, they can be prepared by simple component mixing at room temperature immediately before use. By using this approach, the mRNA could be stored and delivered in a lyophilized form, which ensures greater stability against degradation compared to freezing. As such, lipid SANP may be suitable for the formulation of vaccine platforms.

To investigate the feasibility of this strategy, a panel of commercially available cationic lipids for the formulation of mRNA-loaded SANP will be screened. An extensive physicochemical characterization will be carried out to select the optimal formulations in terms of size, zeta potential, and mRNA encapsulation efficiency, while in vitro and in vivo studies will provide insights into the ability of mRNA-loaded lipid SANP formulations to induce the ectopic expression of the encoded protein and to elicit an immune response.

Benefit for the community

The recent SARS-CoV-2 pandemic outbreak has highlighted the need for the rapid development of novel and effective vaccines for infectious diseases. Among vaccine candidates, lipid non-viral vectors for mRNA vaccines are revolutionizing the vaccine field, as they can be easily scaled up for industrial manufacturing, rapidly developed and, compared to viral vectors, are unable to cause infection or insertional mutagenesis. However, lipid formulation for mRNA-based vaccines often require cold-chain transport and storage, which increases their cost, the risk of vaccine spoilage due to accidents or mishandling and could make these vaccines inaccessible to low- and middle-income countries which lack cold-chain infrastructures.

Lipid SANP technology represents a promising strategy for rapid development and update (e.g. in the case of virus mutations) of RNA-based vaccines. This should also reduce the cost of the RNA-vaccines, for a large diffusion also in third-world countries.

Visit the supervisors lab


Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, McCullough MP, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott A, Flach B, Doria-Rose NA, Corbett KS, Morabito KM, O'Dell S, Schmidt SD, Swanson PA II, Padilla M, Mascola JR, Neuzil KM, Bennett H, Sun W, Peters E, Makowski M, Albert J, Cross K, Buchanan W, Pikaart-Tautges R, Ledgerwood JE, Graham BS, Beigel JH, 2020
An mRNA Vaccine against SARS-CoV-2 - Preliminary Report
N. Engl. J. Med. 383, 1920-1931
Walsh EE, Frenck RW, Jr., Falsey AR, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Mulligan MJ, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Türeci Ö, Tompkins KR, Lyke KE, Raabe V, Dormitzer PR, Jansen KU, Şahin U, Gruber WC, 2020
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates
N. Engl. J. Med. 383, 2439-2450
Campani V, Zappavigna S, Scotti L, Abate M, Porru M, Leonetti C, Caraglia M, De Rosa G, 2020
Hybrid lipid self-assembling nanoparticles for brain delivery of microRNA
Int. J. Pharm. 588, 119693
previous project
next project