Among other things, the present disclosure relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer. In some embodiments, a chirally controlled oligonucleotide composition has any sequence of bases, and/or pattern or base modifications, sugar modifications, backbone modifications and/or stereochemistry, or combination of these elements, described herein.本發明尤其關於選擇設計之對掌性受控寡核苷酸、對掌性受控寡核苷酸組合物，及其製造及使用方法。在一些實施例中，所提供之對掌性受控寡核苷酸組合物提供核酸聚合物之裂解模式不同於參考寡核苷酸組合物。在一些實施例中，所提供之對掌性受控寡核苷酸組合物提供在核酸聚合物之互補序列內的單一位點裂解。在一些實施例中，對掌性受控寡核苷酸組合物具有本文所述之任何鹼基序列，及/或模式或鹼基修飾、糖修飾、主鏈修飾及/或立體化學，或此等要素之組合。
