NPJ vaccinesNov 20, 2025

Producing Functional Antibodies Against a Cell Receptor Using mRNA Lipid Nanoparticle Immunization

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

PAR4- immunization generated functional anti-PAR4 antibodies that inhibited PAR4-mediated platelet aggregation in mice-derived hybridomas.

Evidence

This preclinical antibody-generation study characterized a PAR4-mRNA-LNP formulation, confirmed native glycosylated PAR4 expression on cells, immunized mice, and isolated five inhibitory hybridoma clones.

Caveat

The work shows antibody generation and platelet-aggregation inhibition in preclinical systems, not therapeutic efficacy or safety in thrombotic cardiovascular disease.

Simplified

(GPCRs) are key therapeutic targets for various diseases, such as the thrombin receptor protease-activated receptor 4 (PAR4) involved in thrombotic cardiovascular disorders. However, the structural complexity of native GPCRs hinders recombinant protein production, making peptide-based immunization insufficient for generating high-quality antibodies. Here, we developed a PAR4- vaccine to express native PAR4 in vivo, thereby inducing potent and specific anti-PAR4 antibodies. The PAR4-mRNA-LNP formulation showed 93.44% encapsulation efficiency, an average size of 127.5 nm, and a polydispersity index (PDI) of 0.1033. Native 55-kDa PAR4 protein with complete glycosylation was confirmed on the cell surface using western blotting and flow cytometry. Mice immunized with PAR4-mRNA-LNP produced strong anti-PAR4 antibody responses, as detected by cell-based ELISA. Finally, we established hybridoma cell lines and identified five clones that significantly inhibited PAR4-mediated platelet aggregation. These findings suggest that mRNA-LNP technology can be broadly applied to generate functional anti-GPCR antibodies for therapy.

Key numbers

93.44%

Efficiency of - formulation in encapsulating mRNA.

6 of 6

Antibody Response at 30,000-fold Dilution

Mice showing antibody responses after final immunization .

Functional Antibody Clones Identified

Number of clones that inhibited -mediated .

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Funding

Competing interests

0%of authors

0 of 15

authors report competing interests

15 report none

PubMed

Producing Functional Antibodies Against a Cell Receptor Using mRNA Lipid Nanoparticle Immunization

Abstract

Key numbers

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief

Abstract

Key numbers

Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief