RNA GUIA DE EDIÇÃO PRIME, SISTEMA DE EDIÇÃO PRIME, POPULAÇÃO DE PARTÍCULAS VIRAIS, LNP, E, MÉTODOS DE EDIÇÃO DE UM GENE CFTR E PARA TRATAR FIBROSE CÍSTICA

Claims

1. Prime editing guide RNA (PEgRNA) or one or more polynucleotides encoding PEgRNA, characterized in that the PEgRNA comprises: a) a spacer that is complementary to a search target sequence in a first strand of a CF transmembrane conductance regulator (CFTR) gene, wherein the spacer comprises at its 3' end the SEQ ID NO: 1; b) a gRNA core capable of binding to a Cas9 protein;(ec) an extension arm comprising: i) an editing model comprising at its end 3'as SEQ ID NOs: 127, 131, 133, 134, 135, 136, 137, 138, 139, 140, 141, 144, 175, 177, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 225, 313, 577, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, or 601, and ii) a primer binding site (PBS) comprising at its 5' end a sequence that is a reverse complement of nucleotides 10-14 of SEQ ID NO: 1, wherein the first strand and The second tape and the others complement each other.

2. PEgRNA according to claim 1, characterized in that the spacer comprises at its end 3'as SEQ ID NOS: 7, 13, 19, 25 or 31.

3. PEgRNA according to claim 1, characterized in that the spacer comprises at its 3' end the SEQ ID NO:

19. Petition 870250087642, dated 09 / 26 / 2025, page 761 / 803 2 / 39 4. PEgRNA according to claim 1, characterized in that the spacer is SEQ ID NO:

19.

5. PEgRNA according to any one of claims 1 to 4, characterized in that the PBS has 5 to 19 nucleotides in length.

6. PEgRNA according to any one of claims 1 to 5, characterized in that the PBS comprises at its 5' end ATATT, ATATTT, ATATTTT, ATATTTTCT, ATATTTTCTT (SEQ ID NO: 67), ATATTTTCTTT (SEQ ID NO: 73), ATATTTTCTTTA (SEQ ID NO: 79), ATATTTTCTTTAA (SEQ ID NO: 85), ATATTTTCTTTAAT (SEQ ID NO: 91), ATATTTTCTTTAATG (SEQ ID NO: 97), ATATTTTCTTTAATGG (SEQ ID NO: 103), ATATTTTCTTTAATGGT (SEQ ID NO: 109), ATATTTTCTTTAATGGTG (SEQ ID NO: 115), or ATATTTTCTTTAATGGTGC (SEQ ID NO: 121), wherein T indicates the presence of a nucleotide of uridine.

7. PEgRNA according to any one of claims 1 to 5, characterized in that the PBS comprises at its 5' end ATATTTTC, ATATTTTCTT (SEQ ID NO: 67), ATATTTTCTTTA (SEQ ID NO: 79), ATATTTTCTTTAATG (SEQ ID NO: 97), or ATATTTTCTTTAATGG (SEQ ID NO: 103), wherein T indicates the presence of a uridine nucleotide.

8. PEgRNA according to any one of claims 1 to 5, characterized in that PBS is ATATTTTC, ATATTTTCTT (SEQ ID NO: 67), ATATTTTCTTTA (SEQ ID NO: 79), ATATTTTCTTTAATG (SEQ ID NO: 97), or ATATTTTCTTTAATGG (SEQ ID NO: 103), wherein T indicates the presence of a uridine nucleotide.

9. PEgRNA according to any of claims 1 to 8, wherein the edition model comprises at its end 3'SEQ ID Nos: 133, 134, 135, 136, 137, 138, 139, 140, 141, 180, 181, 182, 183, 184, Petition 870250087642, dated 09 / 26 / 2025, p. 762 / 803 3 / 39 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 577, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, or 601.

10. PEgRNA according to any one of claims 1 to 8, characterized in that the edition model is SEQ ID NOS: 133, 134, 135, 136, 137, 138, 139, 140, 141, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 577, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, or 601.

11. PEgRNA according to claim 1, characterized in that it has a sequence comprising SEQ ID Nos: 879, 988, 1032, 1041, 1042, 1058, 1067, 1068, 1069, 1087, 1098, 1099, 1100, 1125, 1176, 1177, 1178, 1179, 1180, 1181, 1182, 1183, 1184, 1185, 1186, 1187, 1188, 1225, 1243, 1244, 1245, 1354, 1406, 1407, 1426, 1427, 1428, 1429, 1430, 1431, 1432, 1433, 1434, 1435, 1436, 1437, 1438, 1439, 1440, 1441, 1442, 1443, 1444, 1445, 1446, 1447, 1448, 1449, 1450, 1451, 1452, 1453, 1454, 1455, 1456, 1457, 1458, 1459, 1460, 1461, 1462, 1463, 1464, 1465, 1466, 1467 1468, 1504, 2274, 2275, 2276, 2277, 2278, 2279, 2280, 2281, 2282, 2283, 2284, 2285, 2286, 2287, 2288, 2289, 2290, 2291, 2292, 2293, 2294, 2295, or 2296.

12. PEgRNA according to claim 1, characterized in that it has a sequence consisting of the following SEQ ID numbers: 879, 988, 1032, 1041, 1042, 1058, 1067, 1068, 1069, 1087, 1098, 1099, 1100, 1125, 1176, 1177, 1178, 1179, 1180, 1181, 1182, 1183, 1184, 1185, 1186, 1187, 1188, 1225, 1243, 1244, 1245, 1354, 1406, 1407, 1426, 1427, 1428, 1429, 1430, 1431, 1432, 1433, 1434, 1435, 1436, 1437, 1438, 1439, 1440, 1441, 1442, 1443, 1444, 1445, 1446, 1447, 1448, 1449, 1450, 1451, 1452, 1453, Petition 870250087642, dated 09 / 26 / 2025, p. 763 / 803 4 / 39 1454, 1455, 1456, 1457, 1458, 1459, 1460, 1461, 1462, 1463, 1464, 1465, 1466, 1467, 1468, 1504, 2274, 2275, 2276, 2277, 2278, 2279, 2280, 2281, 2282, 2283, 2284, 2285, 2286, 2287, 2288, 2289, 2290, 2291, 2292, 2293, 2294, 2295, or 2296.

13. Primer editing guide RNA (PEgRNA) or one or more polynucleotides encoding PEgRNA, characterized in that the PEgRNA comprises: a) a spacer that is complementary to a search target sequence in a first strand of a CF transmembrane conductance regulator (CFTR) gene, wherein the spacer comprises at its 3' end SEQ ID NO: 2; b) a gRNA core capable of binding to a Cas9 protein; and c) an extension arm comprising: i) an editing template comprising at its 3' end SEQ ID NO: 226, and ii) a primer binding site (PBS) comprising at its 5' end a sequence that is a reverse complement of nucleotides 10-14 of SEQ ID NO: 2, wherein the first strand and the second strand are complementary to each other.

14. PEgRNA according to claim 13, characterized in that the spacer comprises at its end 3'as SEQ ID NOs: 8, 14, 20, 26 or 32.

15. PEgRNA according to claim 13, characterized in that the spacer comprises at its 3' end the SEQ ID NO:

20.

16. PEgRNA according to claim 13, characterized in that the spacer is SEQ ID NO:

20. Petition 870250087642, dated 09 / 26 / 2025, p. 764 / 803 5 / 39 17. PEgRNA according to any one of claims 13 to 16, characterized in that the PBS is 5 to 19 nucleotides long.

18. PEgRNA according to any one of claims 13 to 17, characterized in that the PBS comprises at its 5' end ATGGT, ATGGTG, ATGGTGGC, ATGGTGCCA, ATGGTGCCAG (SEQ ID NO: 68), ATGGTGCCAGG (SEQ ID NO: 74), ATGGTGCCAGGC (SEQ ID NO: 80), ATGGTGCCAGGCA (SEQ ID NO: 86), ATGGTGCCAGGCAT (SEQ ID NO: 92), ATGGTGCCAGGCATA (SEQ ID NO: 98), ATGGTGCCAGGCATAA (SEQ ID NO: 104), ATGGTGCCAGGCATAAT (SEQ ID NO: 110), ATGGTGCCAGGCATAATC (SEQ ID NO: 116), or ATGGTGCCAGGCATAATCC (SEQ ID NO: 122), wherein T indicates the presence of a nucleotide of uridine.

19. PEgRNA according to any one of claims 13 to 17, characterized in that the PBS comprises at its 5' end SEQ ID NO: 68, wherein T indicates the presence of a uridine nucleotide.

20. PEgRNA according to any one of claims 13 to 17, characterized in that PBS is SEQ ID NO: 68, where T indicates the presence of a uridine nucleotide.

21. PEgRNA according to claim 13, characterized in that it has a sequence comprising SEQ ID NO:

864.

22. PEgRNA according to claim 13, characterized in that it has a sequence consisting of SEQ ID NO:

864.

23. Prime editing guide RNA (PEgRNA) or one or more polynucleotides encoding PEgRNA, characterized in that the PEgRNA comprises: a) a spacer that is complementary to a target sequence of Petition 870250087642, dated 09 / 26 / 2025, page.765 / 803 6 / 39 search in a first strand of a CF transmembrane conductance regulator (CFTR) gene, wherein the spacer comprises at its 3' end the SEQ ID NO: 3; b) a gRNA core capable of binding to a Cas9 protein; (ec) an extension arm comprising: (i) an editing model comprising at its 3' end the SEQ ID Nos: 345, 348, 541, 544, 546, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, R. 655, 664, 666, 667, 670, 671, 673, 676, 677, 689, 691, 693, 700, 702, 709, 712, 713, 723, 750, 754, 759, 764, 782, 786, 794, 799, 801, 811, 812, 813, 814, 817, 819, 821, 823, 824, or 825, and ii) a primer binding site (PBS) comprising at its 5' end a sequence that is a reverse complement of nucleotides 10-14 of SEQ ID NO: 3, wherein the first strand and the second strand are complementary to each other.

24. PEgRNA according to claim 23, characterized in that the spacer comprises at its end 3'as SEQ ID NOS: 9, 15, 21, 27 or 33.

25. PEgRNA according to claim 23, characterized in that the spacer comprises at its 3' end the SEQ ID NO:

21.

26. PEgRNA according to claim 23, characterized in that the spacer is SEQ ID NO:

21.

27. PEgRNA according to any one of claims 23 to 26, characterized in that the PBS is 5 to 19 nucleotides long. Petition 870250087642, dated 09 / 26 / 2025, pp. 766 / 803 7 / 39 28. PEgRNA according to any one of claims 23 to 27, characterized in that the PBS comprises at its 5' end ATAAT, ATAATC, ATAATCC, ATAATCCA, ATAATCCAG, ATAATCCAGG (SEQ ID NO: 69), ATAATCCAGGA (SEQ ID NO: 75), ATAATCCAGGAA (SEQ ID NO: 81), ATAATCCAGGAAA (SEQ ID NO: 87), ATAATCCAGGAAAA (SEQ ID NO: 93), ATAATCCAGGAAAAC (SEQ ID NO: 99), ATAATCCAGGAAAACT (SEQ ID NO: 105), ATAATCCAGGAAAACTG (SEQ ID NO: 111), ATAATCCAGGAAAACTGA (SEQ ID NO: 117) or ATAATCCAGGAAAACTGAG (SEQ ID NO: 123), where T indicates the presence of a uridine nucleotide.

29. PEgRNA according to any one of claims 23 to 28, characterized in that the PBS comprises at its 5' end ATAATCC, ATAATCCA, ATAATCCAG, ATAATCCAGG (SEQ ID NO: 69), ATAATCCAGGA (SEQ ID NO: 75), ATAATCCAGGAA (SEQ ID NO: 81), ATAATCCAGGAAA (SEQ ID NO: 87), ATAATCCAGGAAAA (SEQ ID NO: 93) or ATAATCCAGGAAAAC (SEQ ID NO: 99) where T indicates the presence of a uridine nucleotide.

30. PEgRNA according to any one of claims 23 to 28, characterized in that PBS is ATAATCC, ATAATCCA, ATAATCCAG, ATAATCCAGG (SEQ ID NO: 69), ATAATCCAGGA (SEQ ID NO: 75), ATAATCCAGGAA (SEQ ID NO: 81), ATAATCCAGGAAA (SEQ ID NO: 87), ATAATCCAGGAAAA (SEQ ID NO: 93) or ATAATCCAGGAAAAC (SEQ ID NO: 99), where T indicates the presence of a uridine nucleotide.

31. PEgRNA according to any of claims 23 to 30, characterized in that the edition model comprises at its end 3'as SEQ ID Nos: 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, Petition 870250087642, dated 09 / 26 / 2025, p. 767 / 803 8 / 39 578, 602, 604, 606, 615, 617, 634, 637, 638, 651, 655, 664, 666, 667, 670, 671, 673, 676, 677, 689, 691, 693, 700, 702, 709, 712, 713, 723, 750, 754, 759, 764, 782, 786, 794, 799, 801, 811, 812, 813, 814, 817, 819, 821, 823, 824, or 825.

32. PEgRNA according to any one of claims 23 to 30, characterized in that the edition model is SEQ ID NOS: 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 578, 602, 604, 606, 615, 617, 634, 637, 638, 651, 655, 664, 666, 667, 670, 671, R. 814, 817, 819, 821, 823, 824, or 825.

33. PEgRNA according to claim 23, characterized in that it has a sequence comprising the SEQ ID Nos: 894, 1494, 1513, 1514, 1525, 1591, 1592, 1593, 1594, 1624, 1633, 1634, 1635, 1657, 1658, 1659, 1660, 1681, 1682, 1683, 1686, 1896, 1905, 1906, 1907, 1926, 1927, 1928, 1929, 1938, 1939, 1940, 1941, 1950, 1951, 1952, 1953, 1970, 1971, 1972, 1973, 1992, 1993, 2002, 2003, 2021, 2022, 2023, 2024, 2039, 2040, 2043, 2049, 2062, 2063, 2064, 2065, 2074, 2075, 2076, 2077, 2086, 2087, 2088, 2089, 1534, 1535, 1536, 1570, 1595, 1604, 1613, 1614, 1636, 1637, 1638 1639, 1661, 1666, 1667, 1676, 1886, 1887, 1888, 1889, 1908, 1909, 1910, 1911, 1930, 1931, 1932, 1933, 1942, 1943, 1944, 1945, 1954, 1955, 1956, 1957, 1984, 1985, 1986, 1987, 2004, 2005, 2006, 2007, 2025, 2026, 2033, 2034, 2050, 2051, 2052, 2053 2066, 2067, 2068, 2069, 2078, 2079, 2080, 2081, 2090, 2091, 2092, 2093, 1571, 1572, 1573, 1582, 1615, 1616, 1617, 1618, 1645, 1654, 1655, 1656, 1677, 1678, 1679, 1680, 1890,1891, 1892, 1893, 1912, 1915, 1916, 1925, 1934, 1935, 1936, 1937, 1946, 1947, 1948, 1949, 1966, 1967, 1968, 1969, 1988, 1989, 1990, 1991, 2008, 2009, 2019, 2020, 2035, 2036, 2037, 2038, 2054, 2055, 2056, 2061, 2070, 2071, 2072, 2073, 2082, 2083 2084, 2085, 2094, 2095, 2096, 2097, Petition 870250087642, dated 09 / 26 / 2025, p. 768 / 803 9 / 39 2098, 2099, 2100, 2101, 2102, 2103, 2104, 2105, 2268, 2269, 2270, 2271, 2272, 2273, 2299, 2300, 2301, 2302, 2303, 2305, 2306, 2307, 2308, 2309, 2310, 2311, 2312, 2313, or 2314.

34. PEgRNA according to claim 23, characterized in that it has a sequence consisting of the following SEQ ID numbers: 894, 1494, 1513, 1514, 1525, 1534, 1535, 1536, 1570, 1571, 1572, 1573, 1582, 1591, 1592, 1593, 1594, 1595, 1604, 1613, 1614, 1615, 1616, 1617, 1618, 1624, 1633, 1634, 1635, 1636, 1637, 1638, 1639, 1645, 1654, 1655, 1656, 1657, 1658, 1659, 1660, 1661, 1666, 1667, 1676, 1677, 1678, 1679, 1680, 1681, 1682, 1683, 1686, 1886, 1887, 1888, 1889, 1890, 1891, 1892, 1893, 1896, 1905, 1906, 1907, 1908, 1909, 1910, 1911, 1912, 1915, 1916, 1925, 1926, 1927, 1928, 1929 1930, 1931, 1932, 1933, 1934, 1935, 1936, 1937, 1938, 1939, 1940, 1941, 1942, 1943, 1944, 1945, 1946, 1947, 1948, 1949, 1950, 1951, 1952, 1953, 1954, 1955, 1956, 1957, 1966, 1967, 1968, 1969, 1970, 1971, 1972, 1973, 1984, 1985, 1986, 1987, 1988 1989, 1990, 1991, 1992, 1993, 2002, 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2019, 2020, 2021, 2022, 2023, 2024, 2025, 2026, 2033, 2034, 2035, 2036, 2037, 2038, 2039, 2040, 20432049, 2050, 2051, 2052, 2053, 2054, 2055, 2056, 2061, 2062, 2063, 2064, 2065, 2066, 2067, 2068, 2069, 2070, 2071, 2072, 2073, 2074, 2075, 2076, 2077, 2078, 2079, 2080, 2081, 2082, 2083, 2084, 2085, 2086, 2087, 2088, 2089, 2090, 2091, 2092, 2093 2094, 2095, 2096, 2097, 2098, 2099, 2100, 2101, 2102, 2103, 2104, 2105, 2268, 2269, 2270, 2271, 2272, 2273, 2299, 2300, 2301, 2302, 2303, 2305, 2306, 2307, 2308, 2309, 2310, 2311, 2312, 2313, or 2314.

35. Prime editing guide RNA (PEgRNA) or one or more polynucleotides encoding PEgRNA, characterized in that the PEgRNA comprises: a) a spacer that is complementary to a search target sequence in a first strand of a CF transmembrane conductance regulator (CFTR) gene, wherein the spacer comprises at its 3' end SEQ ID NO: 4; b) a gRNA core capable of binding to a Cas9 protein; (ec) an extension arm comprising: i) an editing template comprising at its 3' end SEQ ID NO: 222, and ii) a primer binding site (PBS) comprising at its 5' end a sequence that is a reverse complement of nucleotides 10-14 of SEQ ID NO: 4, wherein the first strand and the second strand are complementary to each other.

36. PEgRNA according to claim 35, characterized in that the spacer comprises at its 3' end the SEQ ID NO: 10, 16, 22, 28 or 34.

37. PEgRNA according to claim 35, characterized in that the spacer comprises at its 3' end the SEQ ID NO:

22.

38. PEgRNA according to claim 35, characterized in that the spacer is SEQ ID NO:

22.

39. PEgRNA according to any one of claims 35 to 38, characterized in that the PBS is 5 to 19 nucleotides long.

40. PEgRNA according to any one of claims 35 to 39, characterized in that the PBS comprises at its end 5'GATGA, GATGAA, GATGAAT, GATGAATA, GATGAATAT, GATGAATATA (SEQ ID NO: 70), GATGAATATAG (SEQ ID NO: 76), GATGAATATAGA (SEQ ID NO: 82), GATGAATATAGAT (SEQ ID NO: 88), GATGAATAGATA (SEQ ID NO: Petition 870250087642, dated 09 / 26 / 2025, p. 770 / 803 11 / 39 94), GATGAATAGATAC (SEQ ID NO: 100), GATGAATAGATACA (SEQ ID NO: 106), GATGAATAGATACAG (SEQ ID NO: 112), GATGAATAGATACAGA (SEQ ID NO: 118), or GATGAATAGATACAGAA (SEQ ID NO: 124), where T indicates the presence of a uridine nucleotide.

41. PEgRNA according to any one of claims 35 to 39, characterized in that the PBS comprises at its 5' end SEQ ID NO:

82.

42. PEgRNA according to any one of claims 35 to 39, characterized in that PBS is SEQ ID NO:

82.

43. PEgRNA according to any one of claims 35 to 42, characterized in that the edition model is SEQ ID NO:

222.

44. PEgRNA according to claim 35, characterized in that it has a sequence comprising SEQ ID NO:

880.

45. PEgRNA according to claim 35, characterized in that it has a sequence consisting of SEQ ID NO:

880.

46. ​​Prime editing guide RNA (PEgRNA) or one or more polynucleotides encoding PEgRNA, characterized in that the PEgRNA comprises: a) a spacer that is complementary to a search target sequence in a first strand of a CF transmembrane conductance regulator (CFTR) gene, wherein the spacer comprises at its 3' end the SEQ ID NO: 5; b) a gRNA core capable of binding to a Cas9 protein; and c) an extension arm comprising: i) an editing template comprising at its 3' end the SEQ ID NOs: 178, 223, 227, 309, 311, 314, 316, 318, 320, 321, 322, Petition 870250087642, dated 09 / 26 / 2025, p. 771 / 803 12 / 39 323, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 339, 341, 343, 346, 349, 350, 351, 352, 353, 354, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401,402, 403, 404, 405,406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420,421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435,436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450,451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465,466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480,481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495,496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510,511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525,526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540,542, 545, 547, 572, 574, 576, 579, 603, 605, 607, 608, 609, 610, 611, 612,613, 614, 616, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629,630, 631, 632, 633, 635, 636, 639, 640, 641, 642, 643, 644, 645, 646, 647,648, 649, 650, 652, 653, 654, 656, 657, 658, 659, 660, 661, 662, 663, 665,668, 669, 672, 674,675, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 690, 692, 694, 695, 696, 697, 698, 699, 701, 703, 704, 705, 706, 707, 708, 710, 711, 714, 715, 716, 717, 718, 719, 720, 721, 722, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 751, 752, 753, 755, 756, 757, 758, 760, 761, 762, 763, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 783, 784, 785, 787, 788, 789 790, 791, 792, 793, 795, 796, 797, 798, 800, 802, 803, 804, 805, 806, 807, 808, 809, 810, 815, 816, 818, 820, 822, 2690, 2691, 2692, 2693, 2694, 2695, 2696, 2697, 2698, 2699, 2700, 2701, 2702, 2703, 2704, 2705, 2706, 2707, 2708, 2709, 2710, 2711, 2712, 2713, 2714, 2715, 2716, 2717, 2718, 2719, 2720, 2721, 2722, Petition 870250087642, dated 09 / 26 / 2025, p. 772 / 803 13 / 39 2723, 2724, 2725, 2726, 2727, 2728, 2729, 2730, 2731, 2732, 2733, 2734, 2735, 2736, 2737, 2738, 2739, 2740, 2741, 2742, 2743, 2744, 2745, 2746, 2747,2748, 2749, 2750, 2751, 2752, 2753, 2754, 2755, 2756, 2757,2758, 2759, 2760, 2761, 2762, 2764, 2766, 2768, 2770, 2772, 2774, 2776,2778, 2780, 2782, 2784, 2786, 2788, 2790, 2792, 2794, 2796, 2798, 2800,2802, 2804, 2806, 2808, 2810, 2812, 2814, 2816, 2818, 2820, 2822, 2824,2826, 2828, 2830, 2832, 2834, 2836, 2838, 2840, 2842, 2844, 2846, 2848,2850, 2852, 2854, 2856, 2858, 2860, 2862, 2864, 2866, 2868, 2870, 2872,2874, 2876, 2878, 2880, 2882, 2884, 2886, 2888, 2890, 2891, 2893, 2895,2897, 2898, 2899, 2900, 2901, 2902, 2903, 2904, 2905, 2906, 2907, 2908,2909, 2910, 2911, 2912, 2913, 2914, 2915, 2916, 2917, 2918, 2919, 2920,2921, 2922, 2923, 2924, 2925, 2926, 2927, 2928, 2929, 2930, 2931, 2932,2933, 2934, 2935, 2936, 2937, 2938, 2939, 2940, 2941, 2942, 2943, 2944,2945, 2946, 2947, 2948, 2949, 2950, 2951, 2952, 2953, 2954, 2955, 2956,2957, 2958, 2959, 2960, 2961, 2962, 2963, 2964, 2965, 2966, 2967, 2968,2969, 2970, 2971, 2972, 2973, 2974, 2975, 2976, 2977, 2978, 2979, 2980,2981, 2982, 2983,2984, 2985, 2986, 2987, 2988, 2989, 2990, 2991, 2992, 2993, 2994, 2995, 2996, 3451, 3452, 3453, 3454, 3455, 3456, 3457, 3458, 3459, 3460, 3461, 3462, 3463, 3464, 3465, 3466, 3467, 3468, 3469, 3470, 3471, 3472, 3473, 3474, 3475, 3476, 3477, 3478 3479, 3480, 3481, 3482, 3483, 3484, 3485, 3486, 3487, 3488, 3489, 3490, 3491, 3492, 3493, 3494, 3495, 3496, 3497, 3498, 3499, 3500, 3501, 3502, 3503, 3504, 3505, 3506, 3507, 3508, 3509, 3510, 3511, 3512, 3513, 3514, 3515, 3516, 3517, 3518, 3565, 3566, 3567, 3568, 3569, 3570, 3571, 3572, 3573, 3574, 3575, 3576, 3577, 3578, 3579, 3580, 3581, 3582, 3583, 3584, 3585, 3586, 3587, 3588, 3589, 3590, 3591, 3592, 3593, 3594, 3595, 3596, 3597, 3598, 3599, 3600, 3601, 3602, 3603, 3604, 3605, 3606, 3607, 3608, 3609, 3610, 3611, 3612, 3613, 3614, 3615, 3616, 3617, 3618, 3619, 3620, 3621, 3622, 3623, 3624, 3625, 3626, 3627, 3628, 3629, 3630, 3631, 3632, 3633, 3634, 3635, 3636, 3637, Petition 870250087642, dated 09 / 26 / 2025, p. 773 / 803 14 / 39 3638, 3639, 3640, 3641, 3642,3643, 3644, 3645, 3646, 3647, 3648, 3649, 3650, 3651, 3652, 3653, 3654, 3655, 3656, 3657, 3658, 3659, 3660, 3661, 3662, 3663, 3664, 3665, 3666, 3667, 3668, 3669, 3670, 3671, 3672, 3673, 3674, 3675, 3676, 3677, 3678, 3679, 3680, 3681, 3682, 3683, 3684, 3685, 3686, 3687, 3688, 3689, 3690, 3691, 3692, 3693, 3694, 3695, 3696, 3697, 3698, 3699, 3700, 3701, 3702, 3703, 3704, 3705, 3706, 3707, 3708, 3709, 3710, 3711, 3712, 3713, 3714, 3715, 3716, 3717, 3718, 3719, 3720, 3721, 3722, 3723, 3724, 3725, 3726, 3727, 3728, 3729, 3730, 3731, 3732, 3733, 3734, 3735, 3736, 3737, 3738, 3739, 3740, 3741, 3742, 3743, 3744, 3745, 3746, 3747, 3748, 3749, 3750, 3751, 3752, 3753, 3754, 3755, 3756, 3757, 3758, 3759, 3760, 3761, 3762, 3763, 3764, 3765, 3766, 3767, 3768, 3769, 3770, 3771, 3772, 3773, 3774, 3775, 3776, 3777, 3778, 3779, 3780, 3781, 3782, 3783, 3784, 3785, 3786, 3787, 3788, 3789, 3790, 3791, 3792, 3793, 3794, 3795, 3796, 3797, 3798, 3799, 3800, 3801, 3802, 3803, 3804, 3805, 3806, 3807, 3808, 3809, or 3810,and ii) a primer binding site (PBS) comprising at its 5' end a sequence that is a reverse complement of nucleotides 10-14 of SEQ ID NO: 5, wherein the first strand and the second strand are complementary to each other.

47. PEgRNA according to claim 46, characterized in that the spacer comprises at its 3' end the SEQ ID NOS: 11, 17, 23, 29 or 35.

48. PEgRNA according to claim 46, characterized in that the spacer comprises at its 3' end the SEQ ID NO:

23.

49. PEgRNA according to claim 46, characterized in that the spacer is SEQ ID NO:

23.

50. PEgRNA according to any of the claims in Petition 870250087642, dated 09 / 26 / 2025, pp. 774 / 803 15 / 39 46 to 49, characterized in that the PBS has 5 to 19 nucleotides in length.

51. PEgRNA according to any one of claims 46 to 50, characterized in that the PBS comprises at its 5' end ATGAA, ATGAAT, ATGAATA, ATGAATAT, ATGAATATAG (SEQ ID NO: 71), ATGAATATAGA (SEQ ID NO: 77), ATGAATATAGAT (SEQ ID NO: 83), ATGAATAGATA (SEQ ID NO: 89), ATGAATAGATAC (SEQ ID NO: 95), ATGAATAGATACA (SEQ ID NO: 101), ATGAATAGATACAG (SEQ ID NO: 107), ATGAATAGATACAGA (SEQ ID NO: 113), ATGAATAGATACAGAA (SEQ ID NO: 119), or ATGAATAGATACAGAAG (SEQ ID NO: 125), where T indicates the presence of a uridine nucleotide.

52. PEgRNA according to any one of claims 46 to 50, characterized in that the PBS comprises at its 5' end ATGAATAT, ATGAATATA, ATGAATATAG (SEQ ID NO: 71), ATGAATATAGA (SEQ ID NO: 77), ATGAATATAGAT (SEQ ID NO: 83), ATGAATATAGATA (SEQ ID NO: 89), ATGAATATAGATAC (SEQ ID NO: 95), ATGAATATAGATACA (SEQ ID NO: 101), or ATGAATAGATACAG (SEQ ID NO: 107), where T indicates the presence of a uridine nucleotide.

53. PEgRNA according to any one of claims 46 to 50, characterized in that PBS is ATGAATAT, ATGAATATA, ATGAATATAG (SEQ ID NO: 71), ATGAATATAGA (SEQ ID NO: 77), ATGAATATAGAT (SEQ ID NO: 83), ATGAATATAGATA (SEQ ID NO: 89), ATGAATATAGATAC (SEQ ID NO: 95), ATGAATATAGATACA (SEQ ID NO: 101), or ATGAATATAGATACAG (SEQ ID NO: 107), where T indicates the presence of a uridine nucleotide.

54. PEgRNA in accordance with any of the claims Petition 870250087642, dated 09 / 26 / 2025, page. 775 / 803 16 / 39 46 to 53, characterized by the fact that the edition model comprises at its end 3'as SEQ ID Nos: 320, 322, 323, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 350, 351, 353, 354, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494,495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508,509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523,524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538,539, 540, 579, 603, 605, 607, 608, 609, 610, 611, 612, 613, 614, 616, 618,619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633,635, 636, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 652,653, 654, 656, 657, 658, 659, 660, 661, 662, 663, 665, 668, 669, 672, 674,675, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 690, 692, 694,695, 696, 697, 698, 699, 701, 703, 704, 705, 706, 707, 708, 710, 711, 714,715, 716, 717, 718, 719, 720, 721, 722, 724, 725, 726, 727, 728, 729, 730,731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745,746, 747, 748, 749, 751, 752, 753, 755, 756, 757, 758, 760, 761, 762, 763,765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779,780, 781, 783, 784, 785, 787, 788, 789,790, 791, 792, 793, 795, 796, 797, 798, 800, 802, 803, 804, 805, 806, 807, 808, 809, 810, 815, 816, 818, 820, 822, 2690, 2691, 2692, 2693, 2694, 2695, 2696, 2697, 2698, 2699, 2700, 2701, 2702, 2703, 2704, 2705, 2706, 2707, 2708, 2709, 2710, 2711, 2712, 2713, Petition 870250087642, dated 09 / 26 / 2025, p. 776 / 803 17 / 39 2714, 2715, 2716, 2717, 2718, 2719, 2720, 2721, 2722, 2723, 2724, 2725, 2726, 2727, 2728, 2729, 2730, 2731, 2732, 2733, 2734, 2735, 2736, 2737, 2738, 2739, 2740, 2741, 2742, 2743, 2744, 2745, 2746, 2747, 2748, 2749, 2750, 2751, 2752, 2753, 2754, 2755, 2756, 2757, 2758, 2759, 2760, 2761, 2762, 2764, 2766, 2768, 2770, 2772, 2774, 2776, 2778, 2780, 2782, 2784, 2786, 2788, 2790, 2792, 2794, 2796, 2798, 2800, 2802, 2804, 2806, 2808, 2810, 2812, 2814, 2816, 2818, 2820, 2822, 2824, 2826, 2828, 2830, 2832, 2834, 2836, 2838, 2840, 2842, 2844, 2846, 2848, 2850, 2852, 2854, 2856, 2858, 2860, 2862, 2864, 2866, 2868, 2870, 2872, 2874, 2876, 2878, 2880, 2882, 2884, 2886, 2888, 2890, 2891, 28932895, 2897, 2898, 2899,2900, 2901, 2902, 2903, 2904, 2905, 2906, 2907, 2908, 2909, 2910, 2911,2912, 2913, 2914, 2915, 2916, 2917, 2918, 2919, 2920, 2921, 2922, 2923,2924, 2925, 2926, 2927, 2928, 2929, 2930, 2931, 2932, 2933, 2934, 2935,2936, 2937, 2938, 2939, 2940, 2941, 2942, 2943, 2944, 2945, 2946, 2947,2948, 2949, 2950, 2951, 2952, 2953, 2954, 2955, 2956, 2957, 2958, 2959,2960, 2961, 2962, 2963, 2964, 2965, 2966, 2967, 2968, 2969, 2970, 2971,2972, 2973, 2974, 2975, 2976, 2977, 2978, 2979, 2980, 2981, 2982, 2983,2984, 2985, 2986, 2987, 2988, 2989, 2990, 2991, 2992, 2993, 2994, 2995,2996, 3451, 3452, 3453, 3454, 3455, 3456, 3457, 3458, 3459, 3460, 3461,3462, 3463, 3464, 3465, 3466, 3467, 3468, 3469, 3470, 3471, 3472, 3473,3474, 3475, 3476, 3477, 3478, 3479, 3480, 3481, 3482, 3483, 3484, 3485,3486, 3487, 3488, 3489, 3490, 3491, 3492, 3493, 3494, 3495, 3496, 3497,3498, 3499, 3500, 3501, 3502, 3503, 3504, 3505, 3506, 3507, 3508, 3509,3510, 3511, 3512, 3513, 3514, 3515, 3516, 3517, 3518,3565, 3566, 3567, 3568, 3569, 3570, 3571, 3572, 3573, 3574, 3575, 3576, 3577, 3578, 3579, 3580, 3581, 3582, 3583, 3584, 3585, 3586, 3587, 3588, 3589, 3590, 3591, 3592, 3593, 3594, 3595, 3596, 3597, 3598, 3599, 3600, 3601, 3602, 3603, 3604, 3605, 3606, 3607, 3608, 3609, 3610, 3611, 3612, 3613, 3614, 3615, 3616, 3617, 3618, 3619, 3620, 3621, 3622, 3623, 3624, 3625, 3626, 3627, 3628, Petition 870250087642, dated 09 / 26 / 2025, p. 777 / 803 18 / 39 3629, 3630, 3631, 3632, 3633, 3634, 3635, 3636, 3637, 3638, 3639, 3640, 3641, 3642, 3643, 3644, 3645, 3646, 3647, 3648, 3649, 3650, 3651, 3652, 3653, 3654, 3655, 3656, 3657, 3658, 3659, 3660, 3661, 3662, 3663, 3664, 3665, 3666, 3667, 3668, 3669, 3670, 3671, 3672, 3673, 3674, 3675, 3676, 3677, 3678, 3679, 3680, 3681, 3682, 3683, 3684, 3685, 3686, 3687, 3688, 3689, 3690, 3691, 3692, 3693, 3694, 3695, 3696, 3697, 3698, 3699, 3700, 3701, 3702, 3703, 3704, 3705, 3706, 3707, 3708, 3709, 3710, 3711, 3712, 3713, 3714, 3715, 3716, 3717, 3718, 3719, 3720, 3721, 3722, 3723,3724, 3725, 3726, 3727, 3728, 3729, 3730, 3731, 3732, 3733, 3734, 3735, 3736, 3737, 3738, 3739, 3740, 3741, 3742, 3743, 3744, 3745, 3746, 3747, 3748, 3749, 3750, 3751, 3752, 3753, 3754, 3755, 3756, 3757, 3758, 3759, 3760, 3761, 3762, 3763, 3764, 3765, 3766, 3767, 3768, 3769, 3770, 3771, 3772, 3773, 3774, 3775, 3776, 3777, 3778, 3779, 3780, 3781, 3782, 3783, 3784, 3785, 3786, 3787, 3788, 3789, 3790, 3791, 3792, 3793, 3794, 3795, 3796, 3797, 3798, 3799, 3800, 3801, 3802, 3803, 3804, 3805, 3806, 3807, 3808, 3809, or 3810.

55. PEgRNA according to any one of claims 46 to 53, characterized in that the edition model is SEQ ID NOS: 320, 322, 323, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 350, 351, 353, 354, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500.501, Petition 870250087642, dated 09 / 26 / 2025,p. 778 / 803 19 / 39 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 579, 603, 605, 607, 608, 609, 610, 611, 612, 613, 614, 616, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 635, 636, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 652, 653, 654, 656, 657, 658, 659, 660, 661, 662, 663, 665, 668, 669 672, 674, 675, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 690, 692, 694, 695, 696, 697, 698, 699, 701, 703, 704, 705, 706, 707, 708, 710, 711, 714, 715, 716, 717, 718, 719, 720, 721, 722, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 751, 752, 753, 755, 756, 757, 758, 760, 761, 762, 763, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 783, 784, 785, 787 788, 789, 790, 791, 792,793, 795, 796, 797, 798, 800, 802, 803, 804, 805, 806,807, 808, 809, 810, 815, 816, 818, 820, 822, 2690, 2691, 2692, 2693, 2694, 2695, 2696, 2697, 2698, 2699, 2700, 2701, 2702, 2703, 2704, 2705, 2706,2707, 2708, 2709, 2710, 2711, 2712, 2713, 2714, 2715, 2716, 2717, 2718,2719, 2720, 2721, 2722, 2723, 2724, 2725, 2726, 2727, 2728, 2729, 2730,2731, 2732, 2733, 2734, 2735, 2736, 2737, 2738, 2739, 2740, 2741, 2742,2743, 2744, 2745, 2746, 2747, 2748, 2749, 2750, 2751, 2752, 2753, 2754,2755, 2756, 2757, 2758, 2759, 2760, 2761, 2762, 2764, 2766, 2768, 2770,2772, 2774, 2776, 2778, 2780, 2782, 2784, 2786, 2788, 2790, 2792, 2794,2796, 2798, 2800, 2802, 2804, 2806, 2808, 2810, 2812, 2814, 2816, 2818,2820, 2822, 2824, 2826, 2828, 2830, 2832, 2834, 2836, 2838, 2840, 2842,2844, 2846, 2848, 2850, 2852, 2854, 2856, 2858, 2860, 2862, 2864, 2866,2868, 2870, 2872, 2874, 2876, 2878, 2880, 2882, 2884, 2886, 2888, 2890,2891, 2893, 2895, 2897, 2898, 2899, 2900, 2901, 2902, 2903, 2904, 2905,2906, 2907, 2908,2909, 2910, 2911, 2912, 2913, 2914, 2915, 2916, 2917, 2918, 2919, 2920, 2921, 2922, 2923, 2924, 2925, 2926, 2927, 2928, 2929, 2930, Petition 870250087642, dated 09 / 26 / 2025, p. 779 / 803 20 / 39 2931, 2932, 2933, 2934, 2935, 2936, 2937, 2938, 2939, 2940, 2941, 2942, 2943, 2944, 2945, 2946, 2947, 2948, 2949, 2950, ​​​​2951, 2952, 2953, 2954, 2955, 2956, 2957, 2958, 2959, 2960, 2961, 2962, 2963, 2964, 2965, 2966, 2967, 2968, 2969, 2970, 2971, 2972, 2973, 2974, 2975, 2976, 2977, 2978, 2979, 2980, 2981, 2982, 2983, 2984, 2985, 2986, 2987, 2988, 2989, 2990, 2991, 2992, 2993, 2994, 2995, 2996, 3451, 3452, 3453, 3454, 3455, 3456, 3457, 3458, 3459, 3460, 3461, 3462, 3463, 3464, 3465, 3466, 3467, 3468, 3469, 3470, 3471, 3472, 3473, 3474, 3475, 3476, 3477, 3478, 3479, 3480, 3481, 3482, 3483, 3484, 3485, 3486, 3487, 3488, 3489, 3490, 3491, 3492, 3493, 3494, 3495, 3496, 3497, 3498, 3499, 3500, 3501, 3502, 3503, 3504, 3505, 3506, 3507, 3508, 3509, 3510, 3511, 3512, 3513, 3514, 3515, 3516, 3517, 3518, 3565, 3566, 3567,3568, 3569, 3570, 3571, 3572, 3573,3574, 3575, 3576, 3577, 3578, 3579, 3580, 3581, 3582, 3583, 3584, 3585,3586, 3587, 3588, 3589, 3590, 3591, 3592, 3593, 3594, 3595, 3596, 3597,3598, 3599, 3600, 3601, 3602, 3603, 3604, 3605, 3606, 3607, 3608, 3609,3610, 3611, 3612, 3613, 3614, 3615, 3616, 3617, 3618, 3619, 3620, 3621,3622, 3623, 3624, 3625, 3626, 3627, 3628, 3629, 3630, 3631, 3632, 3633,3634, 3635, 3636, 3637, 3638, 3639, 3640, 3641, 3642, 3643, 3644, 3645,3646, 3647, 3648, 3649, 3650, 3651, 3652, 3653, 3654, 3655, 3656, 3657,3658, 3659, 3660, 3661, 3662, 3663, 3664, 3665, 3666, 3667, 3668, 3669,3670, 3671, 3672, 3673, 3674, 3675, 3676, 3677, 3678, 3679, 3680, 3681,3682, 3683, 3684, 3685, 3686, 3687, 3688, 3689, 3690, 3691, 3692, 3693,3694, 3695, 3696, 3697, 3698, 3699, 3700, 3701, 3702, 3703, 3704, 3705,3706, 3707, 3708, 3709, 3710, 3711, 3712, 3713, 3714, 3715, 3716, 3717,3718, 3719, 3720, 3721, 3722, 3723, 3724, 3725, 3726, 3727, 3728, 3729,3730, 3731, 3732, 3733, 3734, 3735, 3736,3737, 3738, 3739, 3740, 3741, 3742, 3743, 3744, 3745, 3746, 3747, 3748, 3749, 3750, 3751, 3752, 3753, 3754, 3755, 3756, 3757, 3758, 3759, 3760, 3761, 3762, 3763, 3764, 3765, 3766, 3767, 3768, 3769, 3770, 3771, 3772, 3773, 3774, 3775, 3776 3777,3778, Petition 870250087642, dated 09 / 26 / 2025, p. 780 / 803 21 / 39 3779, 3780, 3781, 3782, 3783, 3784, 3785, 3786, 3787, 3788, 3789, 3790, 3791, 3792, 3793, 3794, 3795, 3796, 3797, 3798, 3799, 3800, 3801, 3802, 3803, 3804, 3805, 3806, 3807, 3808, 3809, or 3810.

56. PEgRNA according to claim 46, characterized in that it has a sequence comprising the SEQ ID Nos: 883, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 935, 936, 937, 938, 939, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004 1005, 1006, 1007, 1014, 1015, 1016, 1017, 1018, 1019, 1026, 1078, 1088, 1089, 1101, 1102, 1160, 1161, 1162, 1163, 1164, 1175, 1207, 1208, 1209, 1210, 1211, 1212, 1230, 1231, 1232, 1233, 1242, 1317, 1324, 1335, 1336, 1337, 1338, 1339, 1388, 1389 1390, 1391, 1392, 1393, 1412, 1413, 1414, 1415, 1424, 1425, 1475, 1476, 1485, 1486, 1487, 1488, 1505, 1506, 1507, 1508, 1509, 1510, 1528, 1529, 1530, 1531, 1532, 1533, 15511552, 1553, 1554, 1555, 1556, 1563, 1564, 1565, 1566, 1567, 1568, 1587, 1588, 1589, 1590, 1602, 1603, 1611, 1612, 1625, 1626, 1627, 1628, 1647, 1648, 1649, 1650, 1651, 1652, 1672, 1673, 1674, 1675, 1687, 1688, 1008, 1009, 1010, 1011, 1012, 1013 1020, 1021, 1022, 1023, 1024, 1025, 1103, 1112, 1113, 1114, 1115, 1116, 1189, 1190, 1191, 1192, 1193, 1194, 1213, 1224, 1226, 1227, 1228, 1229, 1318, 1319, 1320, 1321, 1322, 1323, 1340, 1341, 1342, 1343, 1352, 1353, 1394, 1395, 1408, 1409, 1410, 1411, 1469, 1470, 1471, 1472, 1473, 1474, 1489, 1490, 1491, 1492, 1493, 1503, 1511, 1512, 1523, 1524, 1526, 1527, 1545, 1546, 1547, 1548, 1549, 1550, 1557, 1558, 1559, 1560, 1561, 1562, 1569, 1581, 1583, 1584, 1585, 1586, 1605, 1606, 1607, 1608 1609, 1610, 1629, 1630, 1631, 1632, 1644, 1646, 1653, 1665, 1668, 1669, 1670, 1671, 1689, 1690, 1691, 1692, 1693, 1694, Petition 870250087642, dated 09 / 26 / 2025, p. 781 / 803 22 / 39 1695, 1696, 1697, 1698, 1699, 1700, 1707, 1708, 1709, 1710, 1711, 1712, 1719, 1720,1721, 1722, 1723, 1724, 1731, 1732, 1733, 1734, 1735, 1736, 1743, 1744, 1745, 1746, 1747, 1748, 1755, 1756, 1757, 1758, 1759, 1760, 1767, 1768, 1769, 1770, 1771, 1772, 1779, 1780, 1781, 1782, 1783, 1784, 1791, 1792, 1793, 1794, 1795, 1796, 1803, 1804, 1805, 1806, 1807, 1808, 1815, 1816, 1817, 1818, 1819, 1820, 1827, 1828, 1829, 1830, 1831, 1832, 1839, 1840, 1841, 1842, 1843, 1844, 1851, 1852, 1853, 1854, 1855, 1856, 1863, 1864, 1865, 1866, 1867, 1868, 1875, 1876, 1877, 1878, 1879, 1880, 1897, 1898, 1899, 1900, 1901, 1902, 1921, 1922, 1923, 1924, 1958, 1959, 1976, 1977, 1978, 1979, 1980, 1981, 1998, 1999, 2000, 2001, 2012, 2013, 2028, 2029, 2030, 2031, 2032, 2044, 2059, 2060, 2106, 2107, 2108, 2109, 2116, 2117, 2118, 2119, 2120, 2121, 2128, 2129, 2130, 2131, 2132, 2133, 2140, 2141, 2142, 2143, 2144, 2145, 2152, 2153, 2154, 2155, 2156, 2157, 2164, 2165, 2166, 2167, 2168, 2169, 2176, 2177, 2178, 2179, 2180, 2181, 2188, 2189, 2190, 2191, 2192, 2193, 1701, 1702, 1703, 1704, 1705, 1706,1713, 1714, 1715, 1716, 1717, 1718, 1725, 1726, 1727, 1728, 1729, 1730, 1737, 1738, 1739, 1740, 1741, 1742, 1749, 1750, 1751, 1752, 1753, 1754, 1761, 1762, 1763, 1764, 1765, 1766, 1773, 1774, 1775, 1776, 1777, 1778, 1785, 1786, 1787, 1788, 1789, 1790, 1797, 1798, 1799, 1800, 1801, 1802, 1809, 1810, 1811, 1812, 1813, 1814, 1821, 1822, 1823, 1824, 1825, 1826, 1833, 1834, 1835, 1836, 1837, 1838, 1845, 1846, 1847, 1848, 1849, 1850, 1857, 1858, 1859, 1860, 1861, 1862, 1869, 1870, 1871, 1872, 1873, 1874, 1881, 1882, 1883, 1884, 1885, 1895, 1903, 1904, 1917, 1918, 1919, 1920, 1960, 1961, 1962, 1963, 1964, 1965, 1982, 1983, 1994, 1995, 1996, 1997, 2014, 2015, 2016, 2017, 2018, 2027, 2045, 2046, 2047, 2048, 2057, 2058, 2110, 2111, 2112, 2113, 2114, 2115, 2122, 2123, 2124, 2125, 2126, 2127, 2134, 2135, 2136, 2137, 2138, 2139, 2146, 2147, 2148, 2149, 2150, 2151, 2158, 2159, 2160, 2161, 2162, 2163, 2170, 2171, 2172, 2173, 2174, 2175, 2182, 2183, 2184, 2185, 2186, 2187, 2194, 2195, 2196, 2197,2198, 2199, Petition 870250087642, dated 09 / 26 / 2025, p. 782 / 803 23 / 39 2200, 2201, 2202, 2203, 2204, 2205, 2206, 2207, 2208, 2209, 2210, 2211, 2212, 2213, 2214, 2215, 2216, 2217, 2218, 2219, 2220, 2221, 2222, 2223, 2224, 2225, 2226, 2227, 2228, 2229, 2230, 2231, 2232, 2233, 2234, 2235, 2236, 2237, 2238, 2239, 2240, 2241, 2242, 2243, 2244, 2245, 2246, 2247, 2248, 2249, 2250, 2251, 2252, 2253, 2254, 2255, 2256, 2257, 2258, 2259, 2260, 2261, 2262, 2263, 2264, 2265, 2266, 2267, 2297, 2298, 2304, 2997, 2998, 2999, 3000, 3001, 3002, 3003, 3004, 3005, 3006, 3007, 3008, 3009, 3010, 3011, 3012, 3013, 3014, 3015, 3016, 3017, 3018, 3019, 3020, 3021, 3022, 3023, 3024, 3025, 3026, 3027, 3028, 3029, 3030, 3031, 3032, 3033, 3034, 3035, 3036, 3037, 3038, 3039, 3040, 3041, 3042, 3043, 3044, 3045, 3046, 3047, 3048, 3049, 3050, 3051, 3052, 3053, 3054, 3055, 3056, 3057, 3058, 3059, 3060, 3061, 3062, 3063, 3064, 3065, 3066, 3067, 3068, 3069, 3071, 3073, 3075, 3077, 3079, 3081, 3083, 3085, 3087, 3089, 3091, 3093, 30953097, 3099, 3101, 3103, 3105, 3107, 3109, 3111, 3113, 3115,3117, 3119, 3121, 3123, 3125, 3127, 3129, 3131, 3133, 3135, 3137, 3139,3141, 3143, 3145, 3147, 3149, 3151, 3153, 3155, 3157, 3159, 3161, 3163,3165, 3167, 3169, 3171, 3173, 3175, 3177, 3179, 3181, 3183, 3185, 3187,3189, 3191, 3193, 3195, 3197, 3199, 3201, 3203, 3205, 3206, 3207, 3208,3209, 3210, 3211, 3212, 3213, 3214, 3215, 3216, 3217, 3218, 3219, 3220,3221, 3222, 3223, 3224, 3225, 3226, 3227, 3228, 3229, 3230, 3231, 3232,3233, 3234, 3235, 3236, 3237, 3238, 3239, 3240, 3241, 3242, 3243, 3244,3245, 3246, 3247, 3248, 3249, 3250, 3251, 3252, 3253, 3254, 3255, 3256,3257, 3258, 3259, 3260, 3261, 3262, 3263, 3264, 3265, 3266, 3267, 3268,3269, 3270, 3271, 3272, 3273, 3274, 3275, 3276, 3277, 3278, 3279, 3280,3281, 3282, 3283, 3284, 3285, 3286, 3287, 3288, 3289, 3290, 3291, 3292,3293, 3294, 3295, 3296, 3297, 3298, 3299, 3300, 3301, 3302, 3303, 3304,3305, 3306, 3307, 3308, 3309, 3310, 3311, 3312, 3313, 3314, 3315, 3316,3317, 3318, 3319,3320, 3321, 3322, 3323, 3324, 3325, 3326, 3327, 3328, 3329, 3330, 3331, 3332, 3333, 3334, 3335, 3336, 3337, 3338, 3339, 3340, 3341, Petition 870250087642, dated 09 / 26 / 2025, p. 783 / 803 24 / 39 3342, 3343, 3344, 3345, 3346, 3347, 3348, 3349, 3350, 3351, 3352, 3353, 3354, 3355, 3356, 3357, 3358, 3359, 3360, 3361, 3362, 3363, 3364, 3365, 3366, 3367, 3368, 3369, 3370, 3371, 3372, 3373, 3374, 3375, 3376, 3377, 3378, 3811, 3812, 3813, 3814, 3815, 3816, 3817, 3818, 3819, 3820, 3821, 3822, 3823, 3824, 3825, 3826, 3827, 3828, 3829, 3830, 3831, 3832, 3833, 3834, 3835, 3836, 3837, 3838, 3839, 3840, 3841, 3842, 3843, 3844, 3845, 3846, 3847, 3848, 3849, 3850, 3851, 3852, 3853 3854, 3855, 3856, 3857, 3858, 3859, 3860, 3861, 3862, 3863, 3864, 3865, 3866, 3867, 3868, 3869, 3870, 3871, 3872, 3873, 3874, 3875, 3876, 3877, 3878, 3879, 3880, 3881, 3882, 3883, 3884, 3885, 3886, 3887, 3888, 3889, 3890, 3891, 3892, 3893, 3894, 3895, 3896, 3897, 3898, 3899, 3900, 3901, 3902, 3903, 3904, 3905, 3906, 3907, 3908, 3909, 3910,3911, 3912, 3913, 3914, 3915, 3916, 3917, 3918, 3919, 3920, 3921, 3922, 3923, 3924, 3925, 3926, 3927, 3928, 3929, 3930, 3931, 3932, 3933, 3934, 3935, 3936, 3937, 3938, 3939, 3940, 3941, 3942, 3943, 3944, 3945, 3946, 3947, 3948, 3949, 3950, 3951, 3952, 3953, 3954, 3955, 3956, 3957, 3958, 3959, 3960, 3961, 3962, 3963, 3964, 3965, 3966, 3967, 3968, 3969, 3970, 3971, 3972, 3973, 3974, 3975, 3976, 3977, 3978, 3979, 3980, 3981, 3982, 3983, 3984, 3985, 3986, 3987, 3988, 3989, 3990, 3991, 3992, 3993, 3994, 3995, 3996, 3997, 3998, 3999, 4000, 4001, 4002, 4003, 4004, 4005, 4006, 4007, 4008, 4009, 4010, 4011, 4012, 4013, 4014, 4015, 4016, 4017, 4018, 4019, 4020, 4021, 4022, 4023, 4024, 4025, 4026, 4027, 4028, 4029, 4030, 4031, 4032, 4033, 4034, 4035, 4036, 4037, 4038, 4039, 4040, 4041, 4042, 4043, 4044, 4045, 4046, 4047, 4048, 4049, 4050, 4051, 4052, 4053, 4054, 4055, 4056, 4057, 4058, 4059, 4060, 4061, 4062, 4063, 4064, 4065, 4066, 4067, or 4068.

57. PEgRNA according to claim 46, characterized in that it has a sequence consisting of the SEQ ID Nos: 883, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, Petition 870250087642, dated 09 / 26 / 2025, p. 784 / 803 25 / 39 926, 927, 928, 929, 930, 931, 932, 935, 936, 937, 938, 939, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007, 1008, 1009, 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019, 1020, 1021, 1022, 1023, 1024, 1025, 1026, 1078, 1088, 1089, 1101, 1102 1103, 1112, 1113, 1114, 1115, 1116, 1160, 1161, 1162, 1163, 1164, 1175, 1189, 1190, 1191, 1192, 1193, 1194, 1207, 1208, 1209, 1210, 1211, 1212, 1213, 1224, 1226, 1227, 1228, 1229, 1230, 12311232, 1233, 1242, 1317, 1318, 1319, 1320, 1321, 1322, 1323,1324, 1335, 1336, 1337, 1338, 1339, 1340, 1341, 1342, 1343, 1352, 1353,1388, 1389, 1390, 1391, 1392, 1393, 1394, 1395, 1408, 1409, 1410, 1411,1412, 1413, 1414, 1415, 1424, 1425, 1469, 1470, 1471, 1472, 1473, 1474,1475, 1476, 1485, 1486, 1487, 1488, 1489, 1490, 1491, 1492, 1493, 1503,1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1523, 1524, 1526, 1527,1528, 1529, 1530, 1531, 1532, 1533, 1545, 1546, 1547, 1548, 1549, 1550,1551, 1552, 1553, 1554, 1555, 1556, 1557, 1558, 1559, 1560, 1561, 1562,1563, 1564, 1565, 1566, 1567, 1568, 1569, 1581, 1583, 1584, 1585, 1586,1587, 1588, 1589, 1590, 1602, 1603, 1605, 1606, 1607, 1608, 1609, 1610,1611, 1612, 1625, 1626, 1627, 1628, 1629, 1630, 1631, 1632, 1644, 1646,1647, 1648, 1649, 1650, 1651, 1652, 1653, 1665, 1668, 1669, 1670, 1671,1672, 1673, 1674, 1675, 1687, 1688, 1689, 1690, 1691, 1692, 1693, 1694,1695, 1696, 1697, 1698, 1699, 1700, 1701, 1702, 1703, 1704, 1705, 1706,1707, 1708, 1709,1710, 1711, 1712, 1713, 1714, 1715, 1716, 1717, 1718, 1719, 1720, 1721, 1722, 1723, 1724, 1725, 1726, 1727, 1728, 1729, 1730, 1731, 1732, 1733, 1734, 1735, 1736, 1737, 1738, 1739, 1740, 1741, 1742, 1743, 1744, 1745, 1746, 1747, 1748, 1749, 1750 1751, 1752, 1753, 1754, 1755, 1756, 1757, 1758, 1759, 1760, 1761, 1762, 1763, 1764, 1765, 1766, 1767, 1768, 1769, 1770, 1771, 1772, 1773, 1774, 1775, 1776, 1777, 1778, 1779, Petition 870250087642, dated 09 / 26 / 2025, page. 785 / 803 26 / 39 1780, 1781, 1782, 1783, 1784, 1785, 1792, 1793, 1794, 1795, 1796, 1797, 1804, 1805, 1806, 1807, 1808, 1809, 1816, 1817, 1818, 1819, 1820, 1821, 1828, 1829, 1830, 1831, 1832, 1833, 1840, 1841, 1842, 1843, 1844, 1845, 1852, 1853, 1854, 1855, 1856, 1857, 1864, 1865, 1866, 1867, 1868, 1869, 1876, 1877, 1878, 1879, 1880, 1881, 1898, 1899, 1900, 1901, 1902, 1903, 1922, 1923, 1924, 1958, 1959, 1960, 1977, 1978, 1979, 1980, 1981, 1982, 1999, 2000, 2001, 2012, 2013, 2014, 2029 2030, 2031, 2032, 2044, 2045, 2060, 2106, 2107, 2108,2109, 2110, 2117, 2118, 2119, 2120, 2121, 2122, 2129, 2130, 2131, 2132, 2133, 2134, 2141, 2142, 2143, 2144, 2145, 2146, 2153, 2154, 2155, 2156, 2157, 2158, 2165, 2166, 2167, 2168, 2169, 2170, 2177, 2178, 2179, 2180, 2181, 2182, 2189, 2190, 2191, 2192, 2193, 2194, 2201, 2202, 2203, 2204, 2205, 2206, 2213, 2214, 2215, 2216, 2217, 2218, 2225, 2226, 2227, 2228, 2229, 2230, 2237, 2238, 2239, 2240, 2241, 2242, 2249, 2250, 2251, 2252, 2253, 2254, 2261, 2262, 2263, 2264, 2265, 2266, 2999, 3000, 3001, 3002, 3003, 3004, 1786, 1787, 1788, 1789, 1790, 1791, 1798, 1799, 1800, 1801, 1802, 1803, 1810, 1811, 1812, 1813, 1814, 1815, 1822, 1823, 1824, 1825, 1826, 1827, 1834, 1835, 1836, 1837, 1838, 1839, 1846, 1847, 1848, 1849, 1850, 1851, 1858, 1859, 1860, 1861, 1862, 1863, 1870, 1871, 1872, 1873, 1874, 1875, 1882, 1883, 1884, 1885, 1895, 1897, 1904, 1917, 1918, 1919, 1920, 1921, 1961, 1962, 1963, 1964, 1965, 1976, 1983, 1994, 1995, 1996, 1997, 1998, 2015, 2016, 2017, 2018, 2027, 2028, 2046, 2047,2048, 2057, 2058, 2059, 2111, 2112, 2113, 2114, 2115, 2116, 2123, 2124, 2125, 2126, 2127, 2128, 2135, 2136, 2137, 2138, 2139, 2140, 2147, 2148, 2149, 2150, 2151, 2152, 2159, 2160, 2161, 2162, 2163, 2164, 2171, 2172, 2173, 2174, 2175, 2176, 2183 2184, 2185, 2186, 2187, 2188, 2195, 2196, 2197, 2198, 2199, 2200, 2207, 2208, 2209, 2210, 2211, 2212, 2219, 2220, 2221, 2222, 2223, 2224, 2231, 2232, 2233, 2234, 2235, 2236, 2243, 2244, 2245, 2246, 2247, 2248, 2255, 2256, 2257, 2258, 2259, 2260, 2267, 2297, 2298, 2304, 2997, 2998, 3005, 3006, 3007, 3008, 3009, 3010, Petition 870250087642, dated 09 / 26 / 2025, p. 786 / 803 27 / 39 3011, 3012, 3013, 3014, 3015, 3016, 3017, 3018, 3019, 3020, 3021, 3022, 3023, 3024, 3025, 3026, 3027, 3028, 3029, 3030, 3031, 3032, 3033, 3034, 3035, 3036, 3037, 3038, 3039, 3040, 3041, 3042, 3043, 3044, 3045, 3046, 3047, 3048, 3049, 3050, 3051, 3052, 3053, 3054, 3055, 3056, 3057, 3058, 3059, 3060, 3061, 3062, 3063, 3064, 3065, 3066, 3067, 3068, 3069, 3071, 3073, 3075, 3077, 30793081, 3083, 3085, 3087, 3089, 3091, 3093,3095, 3097, 3099, 3101, 3103, 3105, 3107, 3109, 3111, 3113, 3115, 3117,3119, 3121, 3123, 3125, 3127, 3129, 3131, 3133, 3135, 3137, 3139, 3141,3143, 3145, 3147, 3149, 3151, 3153, 3155, 3157, 3159, 3161, 3163, 3165,3167, 3169, 3171, 3173, 3175, 3177, 3179, 3181, 3183, 3185, 3187, 3189,3191, 3193, 3195, 3197, 3199, 3201, 3203, 3205, 3206, 3207, 3208, 3209,3210, 3211, 3212, 3213, 3214, 3215, 3216, 3217, 3218, 3219, 3220, 3221,3222, 3223, 3224, 3225, 3226, 3227, 3228, 3229, 3230, 3231, 3232, 3233,3234, 3235, 3236, 3237, 3238, 3239, 3240, 3241, 3242, 3243, 3244, 3245,3246, 3247, 3248, 3249, 3250, 3251, 3252, 3253, 3254, 3255, 3256, 3257,3258, 3259, 3260, 3261, 3262, 3263, 3264, 3265, 3266, 3267, 3268, 3269,3270, 3271, 3272, 3273, 3274, 3275, 3276, 3277, 3278, 3279, 3280, 3281,3282, 3283, 3284, 3285, 3286, 3287, 3288, 3289, 3290, 3291, 3292, 3293,3294, 3295, 3296, 3297, 3298, 3299, 3300, 3301, 3302, 3303, 3304, 3305,3306, 3307, 3308, 3309, 3310, 3311,3312, 3313, 3314, 3315, 3316, 3317, 3318, 3319, 3320, 3321, 3322, 3323, 3324, 3325, 3326, 3327, 3328, 3329, 3330, 3331, 3332, 3333, 3334, 3335, 3336, 3337, 3338, 3339, 3340, 3341, 3342, 3343, 3344, 3345, 3346, 3347, 3348, 3349, 3350, 3351, 3352 3353, 3354, 3355, 3356, 3357, 3358, 3359, 3360, 3361, 3362, 3363, 3364, 3365, 3366, 3367, 3368, 3369, 3370, 3371, 3372, 3373, 3374, 3375, 3376, 3377, 3378, 3811, 3812, 3813, 3814, 3815, 3816, 3817, 3818, 3819, 3820, 3821, 3822, 3823, 3824, 3825 3826, 3827, 3828, 3829, 3830, 3831, 3832, 3833, 3834, 3835, 3836, 3837, 3838, 3839, 3840, 3841, 3842, 3843, 3844, 3845, 3846, 3847, 3848, 3849, 3850, 3851, 3852, 3853, 3854, 3855, 3856, 3857, 3858, Petition 870250087642, dated 09 / 26 / 2025, p. 787 / 803 28 / 39 3859, 3860, 3861, 3862, 3863, 3864, 3865, 3866, 3867, 3868, 3869, 3870, 3871, 3872, 3873, 3874, 3875, 3876, 3877, 3878, 3879, 3880, 3881, 3882, 3883, 3884, 3885, 3886, 3887, 3888, 3889, 3890, 3891, 3892, 3893, 3894, 3895, 3896, 3897, 3898, 3899, 3900, 3901, 3902,3903, 3904, 3905, 3906, 3907, 3908, 3909, 3910, 3911, 3912, 3913, 3914, 3915, 3916, 3917, 3918, 3919, 3920, 3921, 3922, 3923, 3924, 3925, 3926, 3927, 3928, 3929, 3930, 3931, 3932, 3933, 3934, 3935, 3936, 3937, 3938, 3939, 3940, 3941, 3942, 3943, 3944, 3945, 3946, 3947, 3948, 3949, 3950, 3951, 3952, 3953, 3954, 3955, 3956, 3957, 3958, 3959, 3960, 3961, 3962, 3963, 3964, 3965, 3966, 3967, 3968, 3969, 3970, 3971, 3972, 3973, 3974, 3975, 3976, 3977, 3978, 3979, 3980, 3981, 3982, 3983, 3984, 3985, 3986, 3987, 3988, 3989, 3990, 3991, 3992, 3993, 3994, 3995, 3996, 3997, 3998, 3999, 4000, 4001, 4002, 4003, 4004, 4005, 4006, 4007, 4008, 4009, 4010, 4011, 4012, 4013, 4014, 4015, 4016, 4017, 4018, 4019, 4020, 4021, 4022, 4023, 4024, 4025, 4026, 4027, 4028, 4029, 4030, 4031, 4032, 4033, 4034, 4035, 4036, 4037, 4038, 4039, 4040, 4041, 4042, 4043, 4044, 4045, 4046, 4047, 4048, 4049, 4050, 4051, 4052, 4053, 4054, 4055, 4056, 4057, 4058, 4059, 4060, 4061, 4062, 4063, 4064, 4065 4066, 4067, or 4068.

58. Prime editing guide RNA (PEgRNA) or one or more polynucleotides encoding PEgRNA, characterized in that the PEgRNA comprises: a) a spacer that is complementary to a search target sequence in a first strand of a CF transmembrane conductance regulator (CFTR) gene, wherein the spacer comprises at its 3' end SEQ ID NO: 6; b) a gRNA core capable of binding to a Cas9 protein; and c) an extension arm comprising: i) an editing template comprising at its end Petition 870250087642, dated 09 / 26 / 2025, p. 788 / 803 29 / 39 3' as SEQ ID Nos: 128, 129, 130, 132, 142, 143, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 176, 179, 224, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 310, 312, 315, 317, 319, 324, 338, 340, 342, 344, 347, 355, 543, 2763, 2765, 2767, 2769, 2771, 2773, 2775, 2777, 2779, 2781, 2783, 2785, 2787, 2789, 2791, 2793, 2795, 2797, 2799, 2801, 2803, 2805, 2807, 2809, 2811, 2813, 2815, 2817, 2819, 2821, 2823, 2825, 2827, 2829, 2831, 2833, 2835, 2837, 2839, 2841, 2843, 2845, 2847, 2849, 2851, 2853, 2855, 2857, 2859, 2861, 2863, 2865, 2867, 2869, 2871, 2873, 2875, 2877, 2879, 2881, 2883, 2885, 2887, 2889, 2892, 2894, 2896, 3519, 3520, 3521, 3522, 3523, 3524, 3525, 3526, 3527, 3528, 3529, 3530, 3531 3532, 3533, 3534, 3535, 3536, 3537, 3538, 3539, 3540, 3541, 3542, 3543, 3544, 3545, 3546, 3547, 3548, 3549, 3550, 3551, 3552, 3553, or 3554,and ii) a primer binding site (PBS) comprising at its 5' end a sequence that is a reverse complement of nucleotides 10-14 of SEQ ID NO: 6, wherein the first strand and the second strand are complementary to each other.

59. PEgRNA according to claim 58, characterized in that the spacer comprises at its end 3'as SEQ ID NOS: 12, 18, 24, 30 or 36.

60. PEgRNA according to claim 58, characterized in that the spacer comprises at its end 3'a SEQ ID NO: 18 or 24. Petition 870250087642, dated 09 / 26 / 2025, pp. 789 / 803 30 / 39 61. PEgRNA according to claim 58, characterized in that the spacer is SEQ ID NO: 18 or 24.

62. PEgRNA according to any one of claims 58 to 61, characterized in that the PBS is 5 to 19 nucleotides long.

63. PEgRNA according to any one of claims 58 to 62, characterized in that the PBS comprises at its 5' end GTGTT, GTGTTT, GTGTTTC, GTGTTTCCT, GTGTTTCCTA (SEQ ID NO: 72), GTGTTTCCTAT (SEQ ID NO: 78), GTGTTTCCTATG (SEQ ID NO: 84), GTGTTTCCTATGA (SEQ ID NO: 90), GTGTTTCCTATGAT (SEQ ID NO: 96), GTGTTTCCTATGATG (SEQ ID NO: 102), GTGTTTCCTATGATGA (SEQ ID NO: 108), GTGTTTCCTATGATGAA (SEQ ID NO: 114), GTGTTTCCTATGATGAAT (SEQ ID NO: 120) or GTGTTTCCTATGATGAATA (SEQ ID NO: 126), wherein T indicates the presence of a uridine nucleotide.

64. PEgRNA according to any one of claims 58 to 62, characterized in that the PBS comprises at its 5' end GTGTTTCC, GTGTTTCCT, GTGTTTCCTA (SEQ ID NO: 72), GTGTTTCCTAT (SEQ ID NO: 78), GTGTTTCCTATG (SEQ ID NO: 84), GTGTTTCCTATGA (SEQ ID NO: 90), GTGTTTCCTATGAT (SEQ ID NO: 96) or GTGTTTCCTATGATG (SEQ ID NO: 102), wherein T indicates the presence of a uridine nucleotide.

65. PEgRNA according to any one of claims 58 to 62, characterized in that PBS is GTGTTTCC, GTGTTTCCT, GTGTTTCCTA (SEQ ID NO: 72), GTGTTTCCTAT (SEQ ID NO: 78), GTGTTTCCTATG (SEQ ID NO: 84), GTGTTTCCTATGA (SEQ ID NO: 90), GTGTTTCCTATGAT (SEQ ID NO: 96) or GTGTTTCCTATGATG (SEQ ID NO: 102), where T indicates the presence of a uridine nucleotide. Petition 870250087642, dated 26 / 09 / 2025, p. 790 / 803 31 / 39 66. PEgRNA according to any one of claims 58 to 65, characterized in that the edition model comprises at its 3' end the SEQ ID NOS: 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 2763, 2765, 2767, 2769, 2771, 2773, 2775, 2777, 2779, 2781, 2783, 2785, 2787, 2789, 2791, 2793, 2795, 2797, 2799, 2801, 2803, 2805, 2807, 2809, 2811, 2813, 2815, 2817, 2819, 2821, 2823, 2825, 2827, 2829, 2831, 2833, 2835, 2837, 2839, 2841, 2843, 2845, 2847, 2849, 2851, 2853, 2855, 2857, 2859, 2861, 28632865, 2867, 2869, 2871, 2873, 2875, 2877, 2879, 2881, 2883, 2885, 2887, 2889, 2892, 2894, 2896, 3519, 3520, 3521, 3522, 3523, 3524, 3525, 3526, 3527, 3528, 3529, 3530, 3531, 3532, 3533, 3534, 3535, 3536, 3537, 3538, 3539, 3540, 3541, 3542, 3543 3544, 3545, 3546, 3547, 3548, 3549, 3550, 3551, 3552, 3553, or 3554.

67. PEgRNA according to any one of claims 58 to 66, characterized in that the edition model is SEQ ID NOS: 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 2763, 2765, 2767, 2769, 2771, 2773, 2775, 2777, 2779, 2781, 2783, Petition 870250087642, dated 09 / 26 / 2025, p.791 / 803 32 / 39 2785, 2787, 2789, 2791, 2793, 2795, 2797, 2799, 2801, 2803, 2805, 2807, 2809, 2811, 2813, 2815, 2817, 2819, 2821, 2823, 2825, 2827, 2829, 2831, 2833, 2835, 2837, 2839, 2841, 2843, 2845, 2847, 2849, 2851, 2853, 2855, 2857, 2859, 2861, 2863, 2865, 2867, 2869, 2871, 2873, 2875, 2877, 2879, 2881, 2883, 2885, 2887, 2889, 2892, 2894, 2896, 3519, 3520, 3521, 3522, 3523, 3524, 3525, 3526, 3527, 3528, 3529, 3530, 3531, 3532, 3533, 3534, 3535, 3536, 3537, 3538, 3539, 3540, 3541, 3542 3543, 3544, 3545, 3546, 3547, 3548, 3549, 3550, 3551, 3552, 3553, or 3554.

68. PEgRNA according to claim 58, characterized in that it has a sequence comprising the SEQ ID Nos: 826, 827, 828, 829, 830, 831, 842, 843, 844, 845, 846, 857, 858, 859, 860, 861, 873, 874, 875, 876, 877, 891, 892, 893, 933, 934, 991, 992, 993, 994, 1027, 1037, 1038, 1039, 1040, 1051, 1052, 1053, 1054, 1064, 1065, 1066, 1070, 1080, 1081, 1082, 1083, 1095, 1096, 1097, 1104, 1118, 1119, 1120, 1121, 1131, 1132, 1133, 1134, 1143, 1144, 1145, 1146, 1155, 1156, 1157, 1158, 1172, 1173, 1174, 1195, 1204, 1205, 1206, 1214, 1223, 1234, 1235, 1236, 1249, 1250, 1251, 1252, 832, 833, 834, 835, 836, 847, 848, 849, 850, 851, 862, 863, 865, 866, 867, 878, 881, 882, 884, 885, 940, 941, 942, 943, 944, 1028, 1029, 1030, 1031, 1043, 1044, 1045, 1046, 1055, 1056, 1057, 1059, 1071, 1072, 1073, 1074, 1084, 1085 1086, 1090, 1105, 1106, 1107, 1108, 1122, 1123, 1124, 1126, 1135, 1136, 1137, 1138, 1147, 1148, 1149, 1150, 1159, 1165, 1166, 1167, 1196, 1197, 1198, 1199, 1215, 1216, 12171218, 1237, 1238, 1239, 1240, 1253, 1254, 1255, 1256, 837, 838, 839, 840, 841, 852, 853, 854, 855, 856, 868, 869, 870, 871, 872, 886, 887, 888, 889, 890, 985, 986, 987, 989, 990, 1033, 1034, 1035, 1036, 1047, 1048, 1049, 1050, 1060, 1061, 1062 1063, 1075, 1076, 1077, 1079, 1091, 1092, 1093, 1094, 1109, 1110, 1111, 1117, 1127, 1128, 1129, 1130, 1139, 1140, 1141, 1142, 1151, 1152, 1153, 1154, 1168, 1169, 1170, 1171, 1200, 1201, 1202, 1203, 1219, 1220, 1221, 1222, 1241, 1246, 1247, 1248 1257, 1258, 1259, 1260, Petition 870250087642, dated 09 / 26 / 2025, p. 792 / 803 33 / 39 1261, 1262, 1263, 1264, 1265, 1266, 1267, 1268, 1269, 1270, 1271, 1272, 1273, 1274, 1275, 1276, 1277, 1278, 1279, 1280, 1281, 1282, 1283, 1284, 1285, 1286, 1287, 1288, 1289, 1290, 1291, 1292, 1293, 1294, 1295, 1296, 1297, 1298, 1299, 1300, 1301, 1302, 1303, 1304, 1305, 1306, 1307, 1308, 1309, 1310, 1311, 1312, 1313, 1314, 1315, 1316, 1325, 1326, 1327, 1328, 1329, 1330, 1331, 1332, 1333, 1334, 1344, 1345, 1346, 1347, 1348, 13491350, 1351, 1355, 1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363,1364, 1365, 1366, 1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375,1376, 1377, 1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387,1396, 1397, 1398, 1399, 1400, 1401, 1402, 1403, 1404, 1405, 1416, 1417,1418, 1419, 1420, 1421, 1422, 1423, 1477, 1478, 1479, 1480, 1481, 1482,1483, 1484, 1495, 1496, 1497, 1498, 1499, 1500, 1501, 1502, 1515, 1516,1517, 1518, 1519, 1520, 1521, 1522, 1537, 1538, 1539, 1540, 1541, 1542,1543, 1544, 1574, 1575, 1576, 1577, 1578, 1579, 1580, 1596, 1597, 1598,1599, 1600, 1601, 1619, 1620, 1621, 1622, 1623, 1640, 1641, 1642, 1643,1662, 1663, 1664, 1684, 1685, 1894, 1913, 1914, 1974, 1975, 2010, 2011,2041, 2042, 3070, 3072, 3074, 3076, 3078, 3080, 3082, 3084, 3086, 3088,3090, 3092, 3094, 3096, 3098, 3100, 3102, 3104, 3106, 3108, 3110, 3112,3114, 3116, 3118, 3120, 3122, 3124, 3126, 3128, 3130, 3132, 3134, 3136,3138, 3140, 3142, 3144, 3146, 3148, 3150, 3152, 3154, 3156, 3158, 3160,3162, 3164,3166, 3168, 3170, 3172, 3174, 3176, 3178, 3180, 3182, 3184, 3186, 3188, 3190, 3192, 3194, 3196, 3198, 3200, 3202, 3204, 3379, 3380, 3381, 3382, 3383, 3384, 3385, 3386, 3387, 3388, 3389, 3390, 3391, 3392, 3393, 3394, 3395, 3396, 3397, 3398, 3399 3400, 3401, 3402, 3403, 3404, 3405, 3406, 3407, 3408, 3409, 3410, 3411, 3412, 3413, 3414, 3415, 3416, 3417, 3418, 3419, 3420, 3421, 3422, 3423, 3424, 3425, 3426, 3427, 3428, 3429, 3430, 3431, 3432, 3433, 3434, 3435, 3436, 3437, 3438, 3439, 3440, 3441, 3442, 3443, 3444, 3445, 3446, 3447, 3448, 3449, or 3450.

69. PEgRNA according to claim 58, characterized Petition 870250087642, dated 09 / 26 / 2025, p. 793 / 803 34 / 39 because it has a sequence consisting of the following SEQ ID numbers: 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 865, 866, 867, 868, 869, 870, 871, 872, 873, 874, 875, 876, 877, 878, 881, 882, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 933, 934, 940, 941, 942, 943, 944, 985, 986, 987, 989, 990, 991, 992, 993, 994, 1027, 1028, 1029, 1030, 1031, 1033, 1034, 1035, 1036, 1037 1038, 1039, 1040, 1043, 1044, 1045, 1046, 1047, 1048, 1049, 1050, 1051, 1052, 1053, 1054, 1055, 1056, 1057, 1059, 1060, 1061, 1062, 1063, 1064, 1065, 1066, 1070, 1071, 1072, 1073, 1074, 1075, 1076, 1077, 1079, 1080, 1081, 1082, 1083, 1084, 1085 1086, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097, 1104, 1105, 1106, 1107, 1108, 1109, 1110, 1111, 1117, 1118, 1119,1120, 1121, 1122, 1123, 1124, 1126, 1127, 1128, 1129, 1130,1131, 1132, 1133, 1134, 1135, 1136, 1137, 1138, 1139, 1140, 1141, 1142,1143, 1144, 1145, 1146, 1147, 1148, 1149, 1150, 1151, 1152, 1153, 1154,1155, 1156, 1157, 1158, 1159, 1165, 1166, 1167, 1168, 1169, 1170, 1171,1172, 1173, 1174, 1195, 1196, 1197, 1198, 1199, 1200, 1201, 1202, 1203,1204, 1205, 1206, 1214, 1215, 1216, 1217, 1218, 1219, 1220, 1221, 1222,1223, 1234, 1235, 1236, 1237, 1238, 1239, 1240, 1241, 1246, 1247, 1248,1249, 1250, 1251, 1252, 1253, 1254, 1255, 1256, 1257, 1258, 1259, 1260,1261, 1262, 1263, 1264, 1265, 1266, 1267, 1268, 1269, 1270, 1271, 1272,1273, 1274, 1275, 1276, 1277, 1278, 1279, 1280, 1281, 1282, 1283, 1284,1285, 1286, 1287, 1288, 1289, 1290, 1291, 1292, 1293, 1294, 1295, 1296,1297, 1298, 1299, 1300, 1301, 1302, 1303, 1304, 1305, 1306, 1307, 1308,1309, 1310, 1311, 1312, 1313, 1314, 1315, 1316, 1325, 1326, 1327, 1328,1329, 1330, 1331, 1332, 1333, 1334, 1344, 1345, 1346, 1347, 1348, 1349,1350, 1351, 1355,1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366, 1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377, 1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387, 1396, 1397, Petition 870250087642, dated 09 / 26 / 2025, page. 794 / 803 35 / 39 1398, 1399, 1400, 1401, 1402, 1403, 1404, 1405, 1416, 1417, 1418, 1419, 1420, 1421, 1422, 1423, 1477, 1478, 1479, 1480, 1481, 1482, 1483, 1484, 1495, 1496, 1497, 1498, 1499, 1500, 1501, 1502, 1515, 1516, 1517, 1518, 1519, 1520, 1521, 1522, 1537, 1538, 1539, 1540, 1541, 1542, 1543, 1544, 1574, 1575, 1576, 1577, 1578, 1579, 1580, 1596, 1597, 1598, 1599, 1600, 1601, 1619, 1620, 1621, 1622, 1623, 1640, 1641, 1642, 1643, 1662, 1663, 1664, 1684, 1685, 1894, 1913, 1914, 1974, 1975 2010, 2011, 2041, 2042, 3070, 3072, 3074, 3076, 3078, 3080, 3082, 3084, 3086, 3088, 3090, 3092, 3094, 3096, 3098, 3100, 3102, 3104, 3106, 3108, 3110, 3112, 3114, 3116, 3118, 3120, 3122, 3124, 3126, 3128, 3130, 3132, 3134, 3136, 3138, 3140, 3142 3144, 3146, 3148, 3150,3152, 3154, 3156, 3158, 3160, 3162, 3164, 3166, 3168, 3170, 3172, 3174, 3176, 3178, 3180, 3182, 3184, 3186, 3188, 3190, 3192, 3194, 3196, 3198, 3200, 3202, 3204, 3379, 3380, 3381, 3382, 3383, 3384, 3385, 3386, 3387, 3388, 3389, 3390, 3391, 3392, 3393, 3394, 3395, 3396, 3397, 3398, 3399, 3400, 3401, 3402, 3403, 3404, 3405, 3406, 3407, 3408, 3409, 3410, 3411, 3412, 3413, 3414, 3415, 3416, 3417, 3418, 3419, 3420, 3421, 3422, 3423, 3424, 3425, 3426, 3427, 3428, 3429, 3430, 3431, 3432, 3433, 3434, 3435, 3436, 3437, 3438, 3439, 3440, 3441, 3442, 3443, 3444, 3445, 3446, 3447, 3448, 3449, or 3450.

70. Prime editing system, characterized in that it comprises: a) pEgRNA or one or more polynucleotides according to any of claims 1 to 69; and b) a nick guide RNA (ngRNA), or one or more polynucleotides encoding ngRNA, comprising: i) an ngRNA spacer that is complementary to a search target sequence on the second strand of the CFTR gene, and ii) an ngRNA core capable of binding to a Cas9 protein. Petition 870250087642, dated 09 / 26 / 2025, pp. 795 / 803 36 / 39 71. Prime editing system according to claim 70, characterized in that the PEgRNA spacer and the ngRNA spacer bind to the CFTR gene within 100 base pairs of each other.

72. Prime editing system according to claim 70, characterized in that it comprises PEgRNA according to any one of claims 35 to 45 or 58 to 69.

73. Prime editing system according to claim 72, characterized in that the ngRNA spacer comprises at its 3' end nucleotides 4-20 of SEQ ID NOS: 2315, 2316, 20, 2317 or 2318.

74. Prime editing system according to claim 73, characterized in that the ngRNA spacer is 17 to 22 nucleotides long.

75. Prime editing system according to any one of claims 72 to 74, characterized in that the ngRNA spacer comprises SEQ ID Nos: 2315, 2316, 20, 2317 or 2318.

76. Prime editing system according to any one of claims 72 to 74, characterized in that the ngRNA spacer is SEQ ID Nos: 2315, 2316, 20, 2317 or 2318.

77. Prime editing system according to claim 72, characterized in that the ngRNA has a sequence comprising the SEQ IDs: 2331, 2335, 2336, 2337 or 2338.

78. Prime editing system according to claim 72, characterized in that the ngRNA has a sequence consisting of the SEQ IDs: 2331, 2335, 2336, 2337 or 2338.

79. Prime editing system according to claim 70, characterized in that it comprises PEgRNA according to any one of claims 46 to 57.

80. Prime editing system according to claim 79, Petition 870250087642, dated 09 / 26 / 2025, pp. 796 / 803 37 / 39 characterized in that the ngRNA spacer comprises at its 3' end nucleotides 4-20 of SEQ ID Nos: 2319, 21, 2320, 2321, 2322, 2323, 2324, 2325, 2326, 2327, 2328, 2329, 3555, 3556, 3557, 3558 or 3559.

81. Prime editing system according to claim 79, characterized in that the ngRNA spacer is 17 to 22 nucleotides long.

82. Prime editing system according to any one of claims 79 to 81, characterized in that the ngRNA spacer comprises the SEQ ID Nos: 2319, 21, 2320, 2321, 2322, 2323, 2324, 2325, 2326, 2327, 2328, 2329, 3555, 3556, 3557, 3558 or 3559.

83. Prime editing system according to any one of claims 79 to 81, characterized in that the ngRNA spacer is the SEQ ID numbers: 2319, 21, 2320, 2321, 2322, 2323, 2324, 2325, 2326, 2327, 2328, 2329, 3555, 3556, 3557, 3558 or 3559.

84. Prime editing system according to claim 79, characterized in that the ngRNA has a sequence comprising the SEQ ID numbers: 2330, 2332, 2333, 2334, 2339, 2340, 2341, 2342, 2343, 2344, 2345, 2346, 3560, 3561, 3562, 3563 or 3564.

85. Prime editing system according to claim 79, characterized in that the ngRNA has a sequence consisting of the SEQ ID numbers: 2330, 2332, 2333, 2334, 2339, 2340, 2341, 2342, 2343, 2344, 2345, 2346, 3560, 3561, 3562, 3563 or 3564.

86. Prime editing system according to any one of claims 70 to 85, characterized in that it further comprises a prime editor, or one or more polynucleotides encoding the prime editor, wherein the prime editor comprises: a) a Cas9 protein, optionally a Cas9 nickase with a nuclease-inactivating mutation in the HNH domain; and Petition 870250087642, dated 09 / 26 / 2025, pp. 797 / 803 38 / 39 b) a reverse transcriptase.

87. Population of viral particles, characterized in that it collectively comprises one or more polynucleotides encoding the prime editing system according to any one of claims 70 to 86.

88. Population of viral particles according to claim 87, characterized in that the viral particles are AAV particles.

89. LNP, characterized in that it comprises the prime editing system, as defined in any one of claims 70 to 86.

90. A method for editing a CFTR gene, the method characterized in that it comprises contacting the CFTR gene with: a) pEgRNA or one or more polynucleotides according to any of claims 1 to 69, and a prime editor or one or more polynucleotides encoding the prime editor, characterized in that the prime editor comprises: i) a Cas9 protein, optionally a Cas9 nickase with a nuclease-inactivating mutation in the HNH domain, and ii) a reverse transcriptase; or b) the prime editing system of claim 86.

91. Method according to claim 90, characterized in that the CFTR gene is in a cell.

92. Method according to claim 90, in which the cell is a mammalian cell.

93. Method according to claim 90, characterized in that the cell is a human cell.

94. Method according to any one of claims 90 to 93, characterized in that the cell is a primary cell.

95. Method according to any of the claims Petition 870250087642, dated 09 / 26 / 2025, pp. 798 / 803 39 / 39 90 to 94, characterized in that the cell is an epithelial cell.

96. Method according to any one of claims 90 to 95, characterized in that the cell is in a subject or obtained from a subject or from a cell bank.

97. Method according to claim 96, characterized in that the subject is a human.

98. Method according to any one of claims 90 to 97, characterized in that CFTR gene contact comprises cell contact with the viral particle population of claim 87 or 88.

99. Method according to any one of claims 90 to 97, characterized in that CFTR gene contact comprises cell contact with the LNP of claim 89.

100. Method for treating cystic fibrosis in a subject in need thereof, the method characterized in that it comprises administering to the subject a) pEgRNA or one or more polynucleotides according to any one of claims 1 to 69, and a prime editor or one or more polynucleotides encoding the prime editor, characterized in that the prime editor comprises: i) a Cas9 protein, optionally a Cas9 nickase with a nuclease-inactivating mutation in the HNH domain, and ii) a reverse transcriptase; b) the prime editing system of claim 86; c) the viral particle population according to claim 87 or 88; or d) the LNP of claim 89.

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