MUTANT HUMAN ANGIOGENIN (ANGIOGENESIS FACTOR WITH SUPERIOR ANGIOGENIN ACTIVITY) GENES THEREFOR AND METHODS OF EXPRESSION

摘要

ABSTRACTSite-specific mutagenesis of a gene for angiogeninproducing DNA sequences encoding mutant proteins havingincreased angiogenic activity are disclosed. Expressionvectors containing these sequences are introduced intohost cells and direct the production of the mutantangiogenic proteins with markedly increased angiogenic andribonucleolytic activity. Replacement of a single aminoacid, the aspartic acid at or corresponding to position116 of angiogenin, with another amino acid includingasparagine, alanine or histidine, yields mutant proteinswith 8 to 15 fold increased ribonucleolytic activitytoward tRNA and rRNA and 10 to 100 fold increasedangiogenic potency in the chorioallantoic membrane assay.The mutant angiogenin proteins of this invention areuseful therapeutic compositions to promote the developmentof a hemovascular network in a mammal or to promote woundhealing, in particular, healing of torn or traumatizedfibrocartilage material.