Generation of Mature DENVs via Genetic Modification and Directed Evolution
Longping V. Tse, Rita M. Meganck, Stephanie Dong, Lily E. Adams, Laura White, Michael L. Mallory, Ramesh Jadi, Aravinda M. de Silva, Ralph S. Baric
Abstract
and are the target for vaccine development. Here, we used multiple strategies, including protein engineering and natural and directed evolution to generate DENV1, -2, -3, and -4 variants that are highly mature without compromising replication efficiency compared to the parental strains. Given the clinical importance of mature DENVs in immunity, this work provides a roadmap for engineering highly mature DENV that could apply to future vaccine development. Our directed-evolution data also shed light on the divergent evolutionary relationship of DENVs between its host and vector.
Topics & Concepts
Directed evolutionBiologyComputational biologyReplication (statistics)GeneticsGeneVirologyMutantMosquito-borne diseases and controlCRISPR and Genetic EngineeringVirus-based gene therapy research