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Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
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Lipid Nanoparticles with Side-Chain Polymer Coating for Targeted mRNA Delivery through Nanobody Attachment
On Ting Choy1, Nicholas L Fletcher1,2,3, Pie Huda1,2,3
1Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.
Bioconjugate Chemistry
|March 26, 2026
Summary
Researchers developed targeted messenger RNA (mRNA) lipid nanoparticles (LNPs) for cancer immunotherapy. Attaching a nanobody to the LNP surface improved delivery to cancer cells, enhancing treatment potential.
Area of Science:
- Biotechnology
- Immunotherapy
- Nanomedicine
Background:
- Messenger RNA (mRNA) therapies have advanced cancer immunotherapy but lack targeted delivery.
- Current lipid nanoparticle (LNP) formulations can cause off-target immune responses and accumulate in the liver.
- Site- and immune-cell-specific delivery is crucial for improving mRNA-LNP efficacy and safety.
Purpose of the Study:
- To investigate bioconjugation strategies for attaching targeting antibodies to polymer-functionalized mRNA-LNPs.
- To enhance site- and immune-cell-specific delivery of therapeutic mRNA-LNPs.
- To evaluate the effectiveness of active targeting for mRNA-LNP platforms.
Main Methods:
- Utilized a side-chain sulfoxide polymer-lipid conjugate (PMSEA-DSPE) for a low-fouling LNP coating.
- Incorporated trans-cyclooctene functionality for conjugation to a tetrazine-functionalized nanobody (9G8) targeting EGFR.
- Compared direct conjugation and post-insertion bioconjugation methods.
Main Results:
- Direct conjugation of the 9G8 nanobody to PMSEA mRNA-LNPs significantly improved cell association.
- Enhanced in vitro transfection efficiency was observed in an EGFR-positive cell line.
- Demonstrated the potential of active targeting for side-chain polymer-coated mRNA-LNP platforms.
Conclusions:
- Active targeting via antibody conjugation can significantly enhance mRNA-LNP delivery and transfection efficiency.
- Direct conjugation is a viable method for creating targeted mRNA-LNPs with polymer coatings.
- This approach holds promise for improving the specificity and efficacy of mRNA-based cancer immunotherapies.
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