Large scale synthesis of messenger RNA

The present invention provides, inter alia, methods for the large scale production of compositions comprising a full-length messenger RNA product that is substantially free of double-stranded RNA as well as compositions produced using such methods and uses thereof. The present invention is based, in part, on the surprising discovery that mRNA products produced by in vitro transcription using SP6 RNA polymerases are substantially free of double stranded RNA. In one aspect, the invention provides a method for large scale production of mRNA products for mRNA therapy without the need for chromatography steps. 本发明尤其提供了用于大规模产生包含基本上不含双链RNA的全长信使RNA产物的组合物的方法以及使用此类方法产生的组合物及其用途。本发明部分地基于以下令人惊奇的发现：使用SP6RNA聚合酶通过体外转录产生的mRNA产物基本上不含双链RNA。在一方面，本发明提供了大规模产生用于mRNA疗法而不需要色谱步骤的mRNA产物的方法。