IMPROVED METHODS FOR ACHIEVING EXPRESSION FROM ALPHAVIRUS VECTORS

摘要

The present invention provides methods and reagents for enhancing alphavirus replication and gene expression in target cells by manipulating the PKR and/or IFN induced antiviral pathways present in the cell. The methods may also be practiced to expand alphavirus tropism to cells that are typically non-permissive, or only poorly so, for alphavirus replication and infection. The methods may be practiced in vitro, ex vivo or in vivo, for example, for the purposes of producing an alphavirus vector stock or a protein of interest in vitro, or for achieving immunogenic or therapeutic effects in a subject in vivo. Also provided are reagents (helper cells, nucleic acid constructs, helper sequences, alphavirus vectors, and the like) for practicing the methods of the invention.