Genome editing of a

1. An isolated fusion protein comprising a nuclease domain and an engineered zinc finger DNA-binding domain, wherein the engineered zinc finger DNA-binding domain binds to a target site in a rat Rosa gene and the engineered zinc finger DNA-binding domain comprises four, five or six zinc finger DNA recognition regions designated and ordered F1 to F4, F1 to F5 or F1 to F6 from N-terminus to C-terminus and further wherein the engineered zinc finger DNA-binding domain comprises the zinc finger DNA recognition regions selected from the group consisting of:

(i) F1: DRSDLSR (SEQ ID NO:38);

F2: RSDDLTR (SEQ ID NO:39);

F3: TSGHLSR (SEQ ID NO:40);

F4: RSDNLSV (SEQ ID NO:41); and

F5: RSANLTR (SEQ ID NO:42);

(ii) F1: QSDHLTK (SEQ ID NO:43);

F2: NSSNLSR (SEQ ID NO:44);

F3: RSDHLTK (SEQ ID NO:45);

F4: NSDHLSR (SEQ ID NO:46); and

F5: RSDHLSR (SEQ ID NO:47);

(iii) F1: RSDHLSE (SEQ ID NO:48);

F2: RSAALAR (SEQ ID NO:49);

F3: RSDHLST (SEQ ID NO:50);

F4: QNAHRIT (SEQ ID NO:51); and

F5: RSAVLSE (SEQ ID NO:52);

(iv) F1: QSGDLTR (SEQ ID NO:17);

F2: TSGSLTR (SEQ ID NO: 18);

F3: RSANLTR (SEQ ID NO:42);

F4: RSDHLTK (SEQ ID NO:45); and

F5: NSDHLSR (SEQ ID NO:46);

(v) F1: RSANLTR(SEQ ID NO:42);

F2: QSGDLTR (SEQ ID NO: 17);

F3: QSGDLTR (SEQ ID NO: 17);

F4: RSANLAR (SEQ ID NO:53); and

F5: RSDNLRE (SEQ ID NO:54);

(vi) F1: RSDHLST (SEQ ID NO:50);

F2: DNRDRIK (SEQ ID NO:55);

F3: RSDTLSE (SEQ ID NO:56);

F4: QSSHLAR (SEQ ID NO:57); and

F5: QNAHRKT (SEQ ID NO:22);

(vii) F1: QSGDLTR (SEQ ID NO:17);

F2: QSGDLTR (SEQ ID NO: 17);

F3: RSDNLTR (SEQ ID NO:58);

F4: RSDNLSE (SEQ ID NO:21); and

F5: QNAHRKT (SEQ ID NO:22);

(viii) F1: DRSDLSR (SEQ ID NO:38);

F2: RSDHLST (SEQ ID NO:50);

F3: DNRDRIK (SEQ ID NO:55);

F4: RSDTLSE (SEQ ID NO:56); and

F5: QSSHLAR (SEQ ID NO:57);

(ix) F1: QSGDLTR (SEQ ID NO:17);

F2: RSDNLTR (SEQ ID NO:58);

F3: RSDNLSE (SEQ ID NO:21);

F4: QNAHRKT (SEQ ID NO:22);

F5: RSDHLSE (SEQ ID NO:48); and

F6: TSSTRKT (SEQ ID NO:59);

(x) F1: TSGNLTR(SEQ ID NO:60);

F2: QSGNLAR (SEQ ID No:61);

F3: RSDALSV (SEQ ID NO:62);

F4: DSSHRTR (SEQ ID NO:63); and

F5: RSDVLSE (SEQ ID NO:64)

(xi) F1: RSDNLSE (SEQ ID NO:21);

F2: QNAHRKT (SEQ ID NO:22);

F3: RSDHLSE (SEQ ID NO:48);

F4: TSSTRKT (SEQ ID NO:59); and

F5: TSGHLSR (SEQ ID NO:40);

(xii) F1: TSGNLTR (SEQ ID NO:60);

F2: QSGNLAR (SEQ ID NO:61);

F3: RSDALSV (SEQ ID NO:62); and

F4: DSSHRTR (SEQ ID NO:63);

(xiii) F1: QRSNLVR (SEQ ID NO:65);

F2: RSDHLTQ (SEQ ID NO:66);

F3: QSGHLQR (SEQ ID NO:67); and

F4: DRSHLAR (SEQ ID NO:68);

(xiv) F1: RSDVLSE (SEQ ID NO:64);

F2: QRNHRTT (SEQ ID NO:69);

F3: TKRSLIE (SEQ ID NO:70);

F4: TSSNLSR (SEQ ID NO:71);

F5: RSDDLSK (SEQ ID NO:25); and

F6: DNRDRIK (SEQ ID NO:55);

(xv) F1: RSDHLSA (SEQ ID NO:72);

F2: QSGHLSR (SEQ ID NO:24);

F3: RSDHLSR (SEQ ID NO:47);

F4: QNDNRIK (SEQ ID NO:73); and

F5: QSGNLAR (SEQ ID NO:61);

(xvi) F1: NNRDLIN (SEQ ID NO:74);

F2: TSSNLSR (SEQ ID NO:71);

F3: RSDVLSE (SEQ ID NO:64);

F4: QRNHRTT (SEQ ID NO:69);

F5: TKRSLIE (SEQ ID NO:70); and

F6: TSSNLSR (SEQ ID NO:71).

2. The fusion protein of claim 1 , wherein the nuclease domain comprises a Type IIS restriction endonuclease cleavage domain or cleavage half-domain.

3. A polynucleotide encoding the isolated fusion protein of claim 1 .

4. An isolated cell comprising the fusion protein of claim 1 .

5. An isolated cell comprising the polynucleotide of claim 3 .

6. The isolated cell of claim 4 , wherein the cell is a rat embryonic stem cell.

7. A composition comprising the isolated fusion protein of claim 1 and a pharmaceutically acceptable excipient.

8. A composition comprising the polynucleotide of claim 3 and an acceptable excipient.

9. A method for cleaving one or more Rosa genes in an isolated rat cell, the method comprising:

introducing, into the isolated rat cell, one or more fusion proteins of claim 1 into the cell, such that the one or more Rosa genes are cleaved.

10. The method of claim 9 , wherein the one or more fusion proteins are introduced by transformation of isolated rat cell with polynucleotides encoding the fusion proteins.

11. A method of introducing an exogenous polynucleotide sequence into the genome of an isolated rat cell, the method comprising cleaving one or more Rosa genes by the method of claim 9 ; and contacting the isolated rat cell with an exogenous polynucleotide sequence; wherein cleavage of the one or more Rosa genes stimulates integration of the exogenous polynucleotide sequences into the genome by homologous recombination.

12. The method of claim 11 , wherein the exogenous polynucleotide sequence is integrated into the genome via nucleic acid replication processes.

13. The method of claim 11 , wherein the exogenous polynucleotide is integrated into the genome via non-homology dependent targeted integration.

14. A method of modifying a Rosa gene sequence in the genome of an isolated rat cell, the method comprising:

cleaving one or more Rosa genes by the method of claim 9 , wherein

(i) a first zinc finger nuclease cleaves at a first cleavage site and a second zinc finger nuclease cleaves at a second cleavage site;

(ii) the Rosa gene sequence is located between the first cleavage site and the second cleavage site;

(iii) cleavage of the first and second cleavage sites results in a modification of the gene sequence by non-homologous end-joining or homology directed repair.

15. The method of claim 14 , wherein the modification comprises a deletion.

16. The method of claim 14 , wherein the modification comprises insertion of an exogenous sequence.

17. A kit comprising the isolated fusion protein of claim 1 .

18. A kit comprising the polynucleotide of claim 3 .

19. The kit of claim 17 , further comprising additional components selected from the group consisting of one or more exogenous sequences, instructions for use, and combinations thereof.

20. The kit of claim 18 , further comprising additional components selected from the group consisting of one or more exogenous sequences, instructions for use, and combinations thereof.