The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A. In some embodiments, the present disclosure provides methods for dosing a hemophilia A patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor VIII polypeptide.本發明尤其提供編碼在哺乳動物細胞中表現之因子VIII變異體之密碼子經更改的多核苷酸。在一些具體實例中，本發明亦提供用於治療A型血友病之哺乳動物基因療法載體及方法。在一些具體實例中，本發明提供用於向A型血友病患者給予編碼因子VIII多肽之多核苷酸(例如密碼子經更改的多核苷酸)的方法。
