Abstract
Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, water-soluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Antibiotic Prophylaxis*
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Antibodies, Neutralizing / administration & dosage*
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Antibodies, Neutralizing / biosynthesis
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Antibodies, Viral / administration & dosage*
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Antibodies, Viral / biosynthesis
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Antiviral Agents / administration & dosage*
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Diarrhea / immunology
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Diarrhea / prevention & control
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Diarrhea / virology
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Humans
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Intestine, Small / pathology
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Intestine, Small / virology
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Mice
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Mice, Inbred BALB C
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Mice, SCID
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Oryza / genetics
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Oryza / metabolism*
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Plants, Genetically Modified / genetics
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Plants, Genetically Modified / metabolism
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Protein Stability
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Rotavirus / immunology
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Rotavirus Infections / immunology
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Rotavirus Infections / prevention & control*
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Rotavirus Infections / virology
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Seeds / genetics
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Seeds / metabolism
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Single-Chain Antibodies / administration & dosage
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Single-Chain Antibodies / biosynthesis
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Solubility
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Virus Shedding
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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Antiviral Agents
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Single-Chain Antibodies