Targeted mRNA Delivery | Cancer Vaccine Technology

Bispecific Antibody-Targeted mRNA-LNP Delivery

Getting mRNA-lipid nanoparticles (LNPs) into a chosen cell type is still the main obstacle for cancer vaccines. Our platform uses bispecific antibodies (BsAbs) to bridge an LNP and a cell surface marker, which takes targeted mRNA delivery beyond the liver.

Unlike conventional approaches that modify the lipid composition or functionalize the LNP surface, which complicates mRNA manufacture and alters nanoparticle properties, our BsAb technology leaves the mRNA-LNP unmodified. This keeps mRNA production simpler while maintaining efficacy. One arm of the bispecific antibody binds to PEG on the LNP surface, while the other arm carries a custom binder that recognises a protein enriched on the target cell. This targeting technology was originally developed by Dr Chris Howard and has since been adapted for cancer vaccine delivery by our team.

mRNA cancer vaccine delivery: bispecific antibody targeting enables personalised mRNA immunotherapy by bridging mRNA-LNP to target cell surfaces

BsAbs form a molecular bridge between mRNA-loaded lipid nanoparticles and target cells.

Key Advantages of the Platform

A flexible, modular platform for targeted mRNA drug delivery.

Efficient Delivery

Bispecific antibodies deliver mRNA-LNPs to specific cell types in vitro and in vivo, improving uptake and cancer vaccine efficacy.

Customisable Targeting

The platform can be retargeted across a broad range of primary cell types by simply substituting the cell-targeting binding region, advancing personalised mRNA medicine development.

Precision & Safety

miRNA binding sites can reduce expression in off-target organs, increasing the precision and safety of targeted mRNA delivery.

Universal Compatibility

The platform is compatible with all current PEG-containing LNPs, requiring no modification to existing nanoparticle formulations.

Streamlined mRNA Manufacture

Separate mRNA-LNP and bispecific antibody production streamlines personalised mRNA manufacture, enabling faster development while keeping each component independently optimisable.

De-risked Application

The application is de-risked as both mRNA-LNPs and antibody technologies are already in extensive clinical use worldwide.

How Targeted mRNA Delivery Works

Two complementary approaches for targeted mRNA-LNP delivery.

1

Pre-mixing

BsAbs are attached to the surface of mRNA-LNPs before administration. One arm binds PEG on the LNP; the other arm is free to engage cell surface proteins upon reaching the target tissue.

2

Pre-targeting

Cells are first exposed to BsAbs that bind to surface proteins. Unmodified mRNA-LNPs are then administered and retained at the target site via the PEG-binding arm. This novel approach preserves LNP properties and achieves superior delivery compared to pre-mixing.

Publication

Dietmair B, Humphries J, Mercer TR, Thurecht KJ, Howard CB, Cheetham SW. Targeted mRNA delivery with bispecific antibodies that tether LNPs to cell surface markers. Molecular Therapy: Nucleic Acids, Vol. 36, June 2025.

Read the Paper →

Targeted mRNA Delivery for Cancer Immunotherapy