Intramuscular Delivery of Replicon RNA Encoding ZIKV-117 Human Monoclonal Antibody Protects against Zika Virus Infection

Molecular Therapy. Methods & Clinical Development
Jesse H ErasmusNeal Van Hoeven

Abstract

Monoclonal antibody (mAb) therapeutics are an effective modality for the treatment of infectious, autoimmune, and cancer-related diseases. However, the discovery, development, and manufacturing processes are complex, resource-consuming activities that preclude the rapid deployment of mAbs in outbreaks of emerging infectious diseases. Given recent advances in nucleic acid delivery technology, it is now possible to deliver exogenous mRNA encoding mAbs for in situ expression following intravenous (i.v.) infusion of lipid nanoparticle-encapsulated mRNA. However, the requirement for i.v. administration limits the application to settings where infusion is an option, increasing the cost of treatment. As an alternative strategy, and to enable intramuscular (IM) administration of mRNA-encoded mAbs, we describe a nanostructured lipid carrier for delivery of an alphavirus replicon encoding a previously described highly neutralizing human mAb, ZIKV-117. Using a lethal Zika virus challenge model in mice, our studies show robust protection following alphavirus-driven expression of ZIKV-117 mRNA when given by IM administration as pre-exposure prophylaxis or post-exposure therapy.

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Citations

Aug 5, 2020·Nature Biomedical Engineering·Pavlo GilchukRobert H Carnahan
Feb 3, 2021·Vaccines·Anna K BlakneyAndrew J Geall
Feb 2, 2021·Acta Tropica·Jonatas Lobato DuarteMarlus Chorilli
Feb 13, 2021·Vaccines·Cailin E DealObadiah J Plante
Apr 20, 2021·Frontiers in Molecular Biosciences·Pobitra BorahDa'san M M Jaradat
Jul 3, 2021·Vaccines·Giuseppe CappellanoAnnalisa Chiocchetti
Jul 23, 2021·International Journal of Biological Macromolecules·Ilana C L MagalhãesMaria Izabel F Guedes
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Aug 17, 2021·Nature Reviews. Materials·Xucheng HouYizhou Dong
Aug 27, 2021·Nature Reviews. Drug Discovery·Namit ChaudharyKathryn A Whitehead

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Datasets Mentioned

BETA
MG758786.1
KU955591

Methods Mentioned

BETA
transfection
enzyme-linked immunosorbent assay
ELISA
ELISAs
Infection
transfections
restriction digest
Assay
PCR

Software Mentioned

RStudio
Inbios
GraphPad Prism

Related Concepts

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