Gene editing of anticoagulants

A method of treating a hemophilia,

• the method including administration of a composition for gene manipulation into a subject to be treated,
• wherein the composition for gene manipulation includes
• i) a Cas protein, or a nucleic acid sequence encoding the same;
• and
• ii) a guide RNA, or a nucleic acid sequence encoding the same;
• wherein the guide RNA includes
• iii) a guide domain;
• and
• iv) one or more domains selected from a first complementary domain, a second complementary domain, a linker domain, a proximal domain and a tail domain,
• wherein the guide domain includes a guide sequence capable of forming a complementary bond with a target sequence located in a blood coagulation inhibitory gene,
• wherein the blood coagulation inhibitory gene is AT (antithrombin) gene or TFPI (tissue factor pathway inhibition) gene,
• wherein the guide sequence is one or more guide sequences selected from a SEQ ID NO:425 to 830,
• wherein the complementary bond includes mismatching bonds of 0 to 5.

A composition for gene manipulation including:

• i) a Cas protein, or a nucleic acid sequence encoding the same;
• and
• ii) a guide RNA, or a nucleic acid sequence encoding the same;
• wherein the guide RNA includes
• iii) a guide domain;
• and
• iv) one or more domains selected from a first complementary domain, a second complementary domain, a linker domain, a proximal domain and a tail domain,
• wherein the guide domain includes a guide sequence capable of forming a complementary bond with a target sequence located in a blood coagulation inhibitory gene,
• wherein the blood coagulation inhibitory gene is AT (antithrombin) gene or TFPI (tissue factor pathway inhibition) gene,
• wherein the guide sequence is one or more guide sequences selected from a SEQ ID NO:425 to 830,
• wherein the complementary bond includes mismatching bonds of 0 to 5.

A guide RNA including:

• i) a guide domain;
• and
• ii) one or more domains selected from a first complementary domain, a second complementary domain, a linker domain, a proximal domain and a tail domain,
• wherein the guide domain includes a guide sequence capable of forming a complementary bond with a target sequence located in a blood coagulation inhibitory gene,
• wherein the blood coagulation inhibitory gene is AT (antithrombin) gene or TFPI (tissue factor pathway inhibition) gene,
• wherein the guide sequence is one or more guide sequences selected from a SEQ ID NO:425 to 830,
• wherein the complementary bond includes mismatching bonds of 0 to 5,
• wherein the guide RNA is capable of forming a complex with a Cas protein.