Endonuclease targeting blood coagulation factor viii gene and composition for treating hemophilia comprising same

A composition for correcting an inversion of the blood coagulation factor VIII (F8) gene, the composition comprising:

• (a) RNA-guided endonuclease or a nucleotide sequence encoding the RNA-guided endonuclease;
• and
• (b) guiding RNA specifically recognizing the following nucleotide sequence or a complementary sequence thereof, or a nucleotide encoding the guiding RNA, the specifically recognized nucleotide sequence being a 15- to 25-bp nucleotide sequence included in the nucleotide sequence of SEQ ID NO:
• 4, wherein the 5- to 25-bp nucleotide sequence does not have a nucleotide sequence, which has sequence homology of at least 80% in the nucleotide sequence of SEQ ID NO:
• 4, and at the same time, of which the 5′-N(G/A)G-3′ nucleotide is linked downstream.

A composition for inducing an inversion of the blood coagulation factor VIII (F8) gene, the composition comprising:

• (a) RNA-guided endonuclease or a nucleotide sequence encoding the RNA-guided endonuclease;
• and
• (b) guiding RNA specifically recognizing the following nucleotide sequences or complementary sequences thereof, or a nucleotide encoding the guiding RNA, the specifically recognized nucleotide sequences being a pair of nucleotide sequences selected from the group consisting of:
• (i) the nucleotide sequence of SEQ ID NO:
• 1;
• (ii) the nucleotide sequence of SEQ ID NO:
• 2;
• and
• (iii) a 15- to 25-bp nucleotide sequence present in the 562,975-bp nucleotide sequence between (i) and (ii) on intron 22 of the F8 gene, wherein (iii) does not have a nucleotide sequence, which has sequence homology of at least 80% with (i) or (ii) in the 562,975-bp nucleotide between (i) and (ii), and simultaneously, of which the 5′-N(G/A)G-3′ nucleotide is linked downstream.

A composition for inducing an inversion of the blood coagulation factor VIII (F8) gene, the composition comprising:

• (a) RNA-guided endonuclease or a nucleotide sequence encoding the RNA-guided endonuclease;
• and
• (b) guiding RNA specifically recognizing the following nucleotide sequence or a complementary sequence thereof, or a nucleotide sequence encoding the guiding RNA, the specifically recognized nucleotide sequence being a 15- to 25-bp nucleotide sequence included in the nucleotide sequence of SEQ ID NO:
• 4, wherein the 15- to 25-bp nucleotide sequence does not have a nucleotide sequence, which has sequence homology of at least 80% in the nucleotide sequence of SEQ ID NO:
• 4, and simultaneously, of which the 5′-N(G/A)G-3′ nucleotide is linked downstream.

A composition for inducing an inversion of the blood coagulation factor VIII (F8) gene, the composition comprising a polypeptide comprising the following or a nucleotide sequence encoding the polypeptide:

• (a) a pair of endonucleases;
• and
• (b) a transcription activator-like (TAL) effector domain, which is linked to one of (a) and comprises an amino acid sequence specifically binding to a nucleotide sequence at a first location on the F8 gene;
• and
• (c) a transcription activator-like (TAL) effector domain, which is linked to one of (a) and comprises an amino acid sequence specifically binding to a nucleotide sequence at a second location on the F8 gene, or a nucleotide sequence encoding the effector domain, wherein the first and second locations are separated from each other by a length of 10-20 bp while being 15- to 25-bp in length.