Hybrid nucleic acid sequences for genome engineering

A hybrid nucleic acid sequence comprising at least one RNA nucleic acid sequence, at least one DNA nucleic acid sequence, and:

• (a) a CRISPR nucleic acid sequence, comprising at least one RNA nucleic acid sequence, wherein the CRISPR nucleic acid sequence comprises
• (i) a first sequence portion that is complementary to a first DNA target sequence, and
• (ii) a second sequence portion, wherein the second sequence portion is configured to interact with a CRISPR polypeptide;
• and comprising associated with the CRISPR nucleic acid sequence:
• (b) a repair template nucleic acid sequence comprising a DNA nucleic acid sequence, wherein the repair template nucleic acid sequence comprises at least one portion complementary to a second DNA target sequence, and wherein the repair template nucleic acid sequence is configured to mediate targeted homology directed repair;
• and
• (c) optionally:
• a linker region between the CRISPR nucleic acid sequence and the repair template nucleic acid sequence;
• wherein the hybrid nucleic acid sequence is capable of interacting with a CRISPR polypeptide so that the CRISPR polypeptide can recognize the first DNA target sequence and optionally induce a DNA break, and wherein the hybrid nucleic acid sequence is configured to direct genome engineering through homology directed repair mediated by the repair template nucleic acid sequence at the site of the second DNA target sequence.