The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced specificity and/or efficiency of indel formation, when compared to the first-generation meganuclease HBV 11-12x.26. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or hepatocellular carcinoma.本發明涵蓋識別及裂解B型肝炎病毒(HBV)基因組內之識別序列的經工程化核酸酶。經工程化巨核酸酶可以展現至少一種最佳化特徵，諸如相較於第一代巨核酸酶HBV 11-12x.26時，增強的插入缺失形成特異性和/或效率。另外，本發明涵蓋包含經工程化巨核酸酶蛋白質、編碼經工程化巨核酸酶之核酸的醫藥組合物，及此類組合物用於治療HBV感染或肝細胞癌的用途。
