Molecular therapy. Nucleic acidsOct 19, 2026

Detailed lab testing and body processing of RNA-made PGT121-LS antibody against HIV

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 20, 2026

Abstract

A single intravenous administration of PGT121-LS RNA-LNP was well tolerated in non-human primates over 180 days without anti-drug antibody formation.

Ribonucleic acid-encoded broadly neutralizing antibodies (RibobNAbs) may enable in vivo production of effective antibodies against HIV-1.
All RibobNAb variants demonstrated sub-nanomolar binding to HIV-1 Env and potent neutralization in vitro.
In mice, a single RNA-lipid nanoparticle administration led to in vivo expression of all RibobNAb variants, with PGT121-LS showing a longer half-life than PGT121.
Single intramuscular administration of RibobNAb resulted in the development of anti-drug antibodies after day 14 and lower bioavailability.
The in vivo-expressed PGT121-LS RibobNAb retained the same antiviral functionality as the reference protein.

Simplified

Human immunodeficiency virus (HIV)-1 broadly neutralizing antibodies (bNAbs) have demonstrated clinical efficacy but face manufacturing challenges associated with recombinant protein production and purification. Here, we present a ribonucleic acid (RNA)-encoded bNAb (RibobNAb) platform that enables in vivo antibody production of the clinically validated bNAb PGT121 via lipid nanoparticle (LNP) delivery, supporting rapid evaluation of Fc variants (LS, del294, and LS-del294) in vitro and in vivo. We confirmed expression, sub-nanomolar HIV-1 Env binding, and potent neutralization across all RibobNAb variants in vitro. In mice, single RNA-LNP administrations yielded in vivo expression of all RibobNAb variants, with PGT121-LS exhibiting a prolonged half-life compared with PGT121. In non-human primates (NHPs), a single intravenous administration of PGT121-LS RNA-LNP was well tolerated without anti-drug antibody (ADA) formation over 180 days and resulted in PGT121-LS half-lives comparable to the reference protein. Single intramuscular administration showed RibobNAb expression but resulted in ADA development from day 14 onward and lower bioavailability. In vivo-expressed PGT121-LS RibobNAb retained identical antiviral functionality to PGT121-LS reference protein. An NHP pharmacokinetics model integrating RNA transfection and translation dynamics enabled allometric scaling and first-in-human dose prediction. We highlight RibobNAbs as an alternative to conventional purified protein antibodies for rapid development of bNAb-based therapeutic strategies.

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Detailed lab testing and body processing of RNA-made PGT121-LS antibody against HIV

Abstract

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