Several ribonucleases, including onconase anda-sarcin, are known to be toxic to tumor cells. On the other hand, although its structure is relatedto thatofa-sarcin,RNase T1 is noncytotoxic because of its inability to internalize into tumor cells. In this study, we internalized RNase T1 into human tumor cells via a novel gene transfer reagent, hem-agglutinating virus of Japan (HVJ) envelope vector, which resulted in cell death. This cytotoxicity was drastically increased by pretreatment of HVJ envelope vector with protamine sulfate, and was stronger than that of onconase, which is inphase III human clinical trials as a nonmutagenic cancer chemotherapeutic agent. .
