Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms14630
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Funding
- Takeda Pharmaceuticals New Frontier Science award
- NIAID/NIH
- NIH [P30-AI045008]
- [R01-AI050484]
- [R01-AI084860]
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Monoclonal antibodies are one of the fastest growing classes of pharmaceutical products, however, their potential is limited by the high cost of development and manufacturing. Here we present a safe and cost-effective platform for in vivo expression of therapeutic antibodies using nucleoside-modified mRNA. To demonstrate feasibility and protective efficacy, nucleoside-modified mRNAs encoding the light and heavy chains of the broadly neutralizing anti-HIV-1 antibody VRC01 are generated and encapsulated into lipid nanoparticles. Systemic administration of 1.4mg kg(-1) of mRNA into mice results in similar to 170 mu g ml(-1) VRC01 antibody concentrations in the plasma 24 h post injection. Weekly injections of 1mg kg(-1) of mRNA into immunodeficient mice maintain trough VRC01 levels above 40 mu g ml(-1). Most importantly, the translated antibody from a single injection of VRC01 mRNA protects humanized mice from intravenous HIV-1 challenge, demonstrating that nucleoside-modified mRNA represents a viable delivery platform for passive immunotherapy against HIV-1 with expansion to a variety of diseases.
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