The presently disclosed subject matter provides vectors that encode small interfering RNAs (siRNAs) designed to down regulate the expression of hypoxia-inducible genes in a cell. Also provided are compositions and host cells based upon the vectors, as well as methods of using the vectors. The presently disclosed subject matter further provides a method of inhibiting tumor growth infecting cells in a tumor with an adenovirus vector that encodes an siRNA directed against the hypoxia-inducible factor 1.alpha. (HIF-1.alpha.) gene.