主权项 |
1. A method for inhibiting the proliferation of cancer cells, comprising delivering to the cells an effective amount of an engineered human ribonuclease (RNase 1), wherein said RNase 1 comprises a variant of SEQ ID NO:2, wherein said variant matches SEQ ID NO:2 at all positions other than positions 4, 7, 11, 31, 32, 38, 39, 41, 42, 66, 67, 71, 85-94, 111, and 118 and wherein said variant has at least four amino acid substitutions relative to SEQ ID NO:2 at positions selected from the group consisting of 4, 7, 11, 31, 32, 38, 39, 41, 42, 66, 67, 71, 85-94, 111, and 118, wherein said substitutions include at least:
(a) one amino acid substitution located within residues 85 to 94 of SEQ ID NO:2; (b) the amino acid substitution G38R at residue 38 of SEQ ID NO:2; and (c) two amino acid substitutions at amino acid residues selected from the group consisting of residues 4, 7, 11, 31, 32, 39, 41, 42, 66, 67, 71, 111 and 118 of SEQ ID NO:2. |