An mRNA-based platform for the delivery of pathogen-specific IgA into mucosal secretions

Deal, Cailin E.; Richards, Angelene F.; Yeung, Tracy; Maron, Max J.; Wang, Ziqiu; Lai, Yen-Ting; Fritz, Brian R.; Himansu, Sunny; Narayanan, Elisabeth; Liu, Ding; Koleva, Rositsa; Licht, Stuart; Hsiao, Chiaowen J.; Rajlic, Ivana L.; Koch, Hillary; Kleyman, Michael; Pulse, Mark E.; Weiss, William J.; Doering, Jennifer E.; Lindberg, Samantha K.; Mantis, Nicholas J.; Carfi, Andrea; Plante, Obadiah J.

doi:10.1016/j.xcrm.2023.101253

Cited by 7 publications

(1 citation statement)

References 51 publications

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“…While liquid, aerosolized or nebulized delivery of antibodies and nanobodies into the lungs is well established, especially in the wake of the COVID-19 pandemic (Leyva-Grado et al, 2015; Parray et al, 2021; Rong et al, 2020a; Rong et al, 2020b; Streblow et al, 2023), getting them into the intracellular compartment to function as intrabodies is a different matter altogether. However, great strides have been made in the use of mRNA-based platforms for delivery of pathogen and toxin-specific IgG and sdAbs into mucosal tissues, including the lung (Deal et al, 2023; Panova et al, 2023; Tai et al, 2023; Thran et al, 2017). At the same time, methods for optimizing intracellular V H H expression have been elucidated (Dingus et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication

Czajka,

Vance,

Song

et al. 2024

Preprint

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Expression of camelid-derived, single-domain antibodies (VHHs) within the cytoplasm of mammalian cells as “intrabodies” has opened-up novel avenues for medical countermeasures against fast-acting biothreat agents. In this report, we describe a heterodimeric intrabody that renders Vero cells virtually impervious to ricin toxin (RT), a potent Category B ribosome-inactivating protein (RIP). The intrabody consists of two structurally defined VHHs that target distinct epitopes on RT’s enzymatic subunit (RTA): V9E1 targets RTA’s P-stalk recruitment site, and V2A11 targets RTA’s active site. Resistance to RT conferred by the biparatopic VHH construct far exceeded that of either of the VHHs alone and effectively inhibited all measurable RT-induced cytotoxictyin vitro. We propose that targeted delivery of bispecific intrabodies to lung tissues may represent a novel means to shield the airways from the effects of inhalational RT exposure.

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Section: Discussionmentioning

confidence: 99%

A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication

Czajka,

Vance,

Song

et al. 2024

Preprint

Self Cite

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Health Benefits of Monk Fruit under Traditional Dietary Patterns: Perspective on Immunity and Gut Microbiota Modulatory Functions

Song,

Wei,

et al. 2024

Plant Foods Hum Nutr

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A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication

Czajka,

Vance,

Song

et al. 2024

Biochemistry

View full text Add to dashboard Cite

Expression of camelid-derived, single-domain antibodies (V H Hs) within the cytoplasm of mammalian cells as "intrabodies" has opened up novel avenues for medical countermeasures against fast-acting biothreat agents. In this report, we describe a heterodimeric intrabody that renders Vero cells virtually impervious to ricin toxin (RT), a potent Category B ribosomeinactivating protein. The intrabody consists of two structurally defined V H Hs that target distinct epitopes on RT's enzymatic subunit (RTA): V9E1 targets RTA's P-stalk recruitment site, and V2A11 targets RTA's active site. Resistance to RT conferred by the biparatopic V H H construct far exceeded that of either of the V H Hs alone and effectively inhibited all measurable RT-induced cytotoxicity in vitro. We propose that the targeted delivery of bispecific intrabodies to lung tissues may represent a novel means to shield the airways from the effects of inhalational RT exposure.

show abstract

An mRNA-based platform for the delivery of pathogen-specific IgA into mucosal secretions

Cited by 7 publications

References 51 publications

A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication

A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication

Health Benefits of Monk Fruit under Traditional Dietary Patterns: Perspective on Immunity and Gut Microbiota Modulatory Functions

A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication

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