The invention provides, inter alia, improved replicons and vectors encoding them, where the replicons provide sustained expression of an encoded protein. These replicons comprise flavivirus replicases and heterologous protein coding sequences. The heterologous protein coding sequences are flanked by separation sequences for improved efficacy. These nucleic acids provided by the invention, including self-replicating RNAs provided by the invention, are useful in methods of protein expression, such as for vaccines (e.g., for methods of immunization), as well as expression of therapeutic proteins, such as antibodies (e.g., for methods of treatment).
