The Zika virus is a mosquito-borne disease designated a global public health concern, with more than two billion people at risk. For most people Zika manifests as a mild infection, however, this disease carries significant risks during pregnancy resulting in severe developmental defects in newborns. Currently, there is no vaccine or specific medicine for Zika, therefore rapid interventions for the Zika virus are a pressing global need. Now, a study from researchers at Wistar Institute develops synthetic DNA encoding the potent anti-Zika monoclonal antibody, which effectively controls infection in preclinical studies. The team states their synthetic monoclonal-antibody gene delivery and expression may be effective for conferring preventative protection against Zika infection in high-risk populations. The opensource study is published in the journal Molecular Therapy.
Previous studies have indicated individuals who recover from the Zika virus develop antibodies with the ability to protect against infection by the disease. However, the use of these monoclonal antibodies for preventing infection is costly and challenging due to delivery and manufacturing limitations. Therefore, in vivo delivery of nucleic acid which encodes engineered monoclonal-antibody (maB) genes represents an alternative approach with great potential to alleviate challenges presented by traditional mAb biologics. The current study engineers synthetic DNA encoding the potent anti-Zika monoclonal antibody ZK190 resulted in high production of ZK190 in vivo for weeks to months.
The current study engineers synthetic DNA-encoding mAb (DMAb) cassettes expressing the potent anti-Zika monoclonal antibody ZK190 (DMAb-ZK190), a clone known to bind uniquely to the Zika virus antigen. Results show the synthetic antibody provided 100% protection against mortality and signs of illness in mice exposed to a lethal dose of the Zika virus. Data findings show DMAb-ZK190 also completely protected the mice against testicular damage and atrophy after exposure to either a low or high dose of the Zika virus.
The lab states while Zika virus infection is not lethal in non-human primates, three sequential injections of DMAb-ZK190 in rhesus macaques had a positive effect on controlling infection in all five animals and significantly lowered viral loads in four animals. They observed DMAb-ZK190 achieved high expression levels persisting for more than 10 weeks in mice and more than 3 weeks in non-human primates.
The team surmises they have developed a synthetic DNA-encoded antibody against Zika virus which was shown to be effective in preclinical studies. For the future, researchers state their data demonstrates the feasibility of using synthetic nucleic acid for mAb delivery in non-human primates and supports further development for human translation for multiple disease conditions, including the Zika virus.
Source: Wistar Institute
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