Strong Immune Responses Induced by Direct Local Injections of Modified mRNA-Lipid Nanocomplexes
Open accessAbstract
In vitro transcribed mRNAs hold the promises of many medical applications in disease prevention and treatment, such as replacement or supplement of missing or inadequately expressed endogenous proteins and as preventive vaccines against infectious diseases, therapeutic vaccines, or other protein-based biopharmaceutics for cancer therapy. A safe and efficient delivery system for mRNA is crucial to the success of mRNA therapeutic applications. In this study, we report that InstantFECT, a liposome-based transfection reagent, can pack pseudouridine-incorporated mRNA into nanocomplexes that are highly efficient in mediating in vivo transfection in multiple organs after local delivery. High levels of expression of EGFP and luciferase reporters after intratumoral and intramuscular injections were observed, which lasted for up to 96 hrs. Immunogenicity of antigens encoded by mRNA delivered with nanocomplex was investigated by subcutaneous delivery of modified mRNAs encoding Staphylococcus aureus adenosine synthase A (AdsA) and a model tumor-associated antigen ovalbumin (OVA). Strong T cell responses were provoked by both mRNAs delivered. Therapeutic and protective treatment with the OVA mRNA-liposome nanocomplex significantly inhibited B16-OVA tumor progression and increased mouse survival. There was no sign of obvious toxicity related to the treatment both in tissue culture and in mice. An intravenous injection of the same dosage of the modified mRNA-lipid nanocomplex showed minimal transfection in major organs, indicating an excellent safety feature as the gene transfer occurred only at the injection sites, whereas intravenous (i.v.) injection with the same amount of mRNA complexed with a commercial transfection reagent Trans-IT showed luciferase expression in the spleen. In summary, InstantFECT cationic liposomes provide a safe and efficient in vivo locoregional delivery of mRNA and could be a useful tool for basic research and for the development of mRNA-based therapies.
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Lipid nanoparticle-mRNA vaccines have been reported to induce immune protection against parasitical and bacterial infections.
“Apart from viral infections, lipid nanoparticle–mRNA vaccines have been reported to induce immune protection against parasitical31 and bacterial30,198 infections.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [198]
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- Authors
- Arya, S., Lin, Q., Zhou, N., Gao, X., & Huang, J.-D.
- Affiliations
- University of Hong Kong (HK)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Gao, Xiang
- Huang, Jian-Dong
- Venue
- Molecular Therapy - Nucleic Acids
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 19
- Pages
- 1098-1109
- ISSN
- 2162-2531 (ISSN-L)
- PMC
- PMC7016160
- OpenAlex
- W2999643011
- Cited by
- 39
- References
- 35
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 4 · 2023: 9 · 2022: 4 · 2021: 6 · 2020: 2
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Therapy — Nucleic Acids (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Overseas High-Level Talent of Shenzhen City (KQTD2015033117210153)
- Shenzhen Science and Technology Innovation Committee Basic Science Research Grant (208 JCYJ20170413154523577)
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- mRNA delivery, cationic liposomes, local gene delivery, immunogenicity, ovalbumin, tumor-associated antigens, T cell response, B16-OVA tumor, intratumoral injection, intramuscular injection, mRNA vaccines
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