Cells containing CRISPR hybrid DNA/RNA polynucleotides

A cell comprising:

• (i) a first polynucleotide wherein the first polynucleotide comprises a targeting region and an activating region adjacent to said targeting region;
• and (ii) a second polynucleotide wherein the second polynucleotide comprises an activating region wherein the activating region comprises DNA and a sequence that is complementary to a sequence in said activating region of the first polynucleotide, wherein said activating region of the first polynucleotide and said activating region of the second polynucleotide are capable of hybridizing to each other to form an activating duplex region, and wherein said activating duplex region is capable of binding with a site-directed polypeptide selected from the group consisting of a Cas9, a Cas9 with reduced nuclease activity, a Cas9 with nickase activity, a Cas9 with no nuclease activity, and a fusion protein comprising a Cas9 domain, wherein the Cas9 domain is capable of binding with the activating duplex region and wherein the fusion protein further comprises a domain from a polypeptide other than Cas9.