Optimized minizymes and miniribozymes and uses thereof

{
  "publication_number": "US6277634B1",
  "country": "US",
  "kind": "B1",
  "title": "Optimized minizymes and miniribozymes and uses thereof",
  "abstract": "This invention is directed to improved catalytic compounds, minizymes and miniribozymes, capable of hybridizing with a target RNA to be cleaved. The minizymes and miniribozymes and compositions of the present invention may be used in vitro or in vivo. They may be used as diagnostic or therapeutic agents.",
  "claims": [
    "1. A compound having the formula: 3′ (X) n -(Seq. ID No. 51)-(T/U) b - G - (X) n -(Seq. ID No. 52)-(X) n′ 5′ wherein each X represents a nucleotide which may be the same or different and may be modified in its sugar, base or phosphate; wherein each of A, C, G, U, and T represents a nucleotide which may be substituted or modified in its sugar, base or phosphate; wherein (T/U) - (T/U) b - G represents T - (T) b - G or U - (U) b - G, with the proviso that b represents an integer which is 3, 4 or 5; wherein each of (X) n and (X) n′, represents an oligonucleotide having a predetermined sequence which is capable of hybridizing with an RNA target sequence; wherein each of n and n′ represents an integer which defines the number of nucleotides in the oligonucleotide; wherein each solid line represents a covalent bond between the nucleotides located on either side thereof; and wherein a represents an integer which defines a number of nucleotides with the proviso that a may be 0 or 1 and if 0, the A located 5′ of (X) a is bonded to the G located 3′ of (X) a.",
    "2. The compound of claim 1, wherein the oligonucleotide 3′-(X) n - is 3′-(X) n−1 - A -.",
    "3. The compound of claim 1, wherein the oligonucleotide 3′-(X) n - is 3′-(X) n−2 - C - A -.",
    "4. A compound having the formula: 3′ (X) n -(Seg. ID No. 53)-(T/U) b - G - (X) a -(Seq. ID NO. 52)-(X) n′ 5′ wherein each X represents a nucleotide which may be the same or different and Q represents guanylate or deoxyguanylate and both of which may be modified in their sugar, base or phosphate; wherein each of A, C, G, U, and T represents a nucleotide which may be substituted or modified in its sugar, base or phosphate; wherein (T/U) - (T/U) b - Q represents T - (T) b - Q or U - (U) b - Q, with the proviso that b represents an integer which is 3, 4 or 5; wherein each of (X) n−1 - A and (X) n′ represents an oligonucleotide having a predetermined sequence which is capable of hybridizing with an RNA target sequence; wherein each of n and n′ represents an integer which defines the number of nucleotides in the cligonucleotide such that (X) n−1 - A and (X) n′ are sufficient to hybridize to the target sequence; wherein each solid line represents a covalent bond between the nucleotides located on either side thereof; and wherein a represents an integer which defines a number of nucleotides with the proviso that a may be 0 or 1 and if 0, the A located 5′ of (X) a is bonded to the Q located 3′ of (X) a.",
    "5. The compound of claim 4, wherein the oligonucleotide 3′-(X) n−1 - A is 3′-(X) n−2 - C - A -.",
    "6. The compound of claim 4, wherein each X and Q is a deoxyribonucleotide.",
    "7. The compound of claim 4, wherein each X and Q is a ribonucleotide.",
    "8. The compound of claim 1 or 4, wherein (X) a is absent.",
    "9. The compound of claim 1 or 4, wherein the integer b of (T/U) b is equal to 3.",
    "10. The compound of claim 1 or 4, wherein the integer b of (T/U) b is equal to 4.",
    "11. The compound of claim 1, wherein each X is a deoxyribonucleotide.",
    "12. The compound of claim 1, wherein each X is a ribonucleotide.",
    "13. The compound of claim 1 or 4, wherein (T/U) b is a (T) b.",
    "14. The compound of claim 1 or 4, wherein (T/U) b is (U) b.",
    "15. A compound having the formula: 3′ (X) n -(Seq. ID NO. 54)-(T/U) b - G - (X) a -(Seq. ID NO. 52)-(X) n′ 5′ wherein each X represents a nucleotide which may be the same or different and may be substituted or modified in its sugar, base or phosphate; wherein each of A, C, G, U, and T represents a nucleotide which may be modified in its sugar, base or phosphate; wherein C - (T/U) b - G represents C - (T) b - G or C - (U) b - G, with the proviso that b represents an integer which is 3, 4 or 5; wherein each of (X) n and (X) n′ represents an oligonucleotide having a predetermined sequence which is capable of hybridizing with an RNA target sequence; wherein each of n and n′ represents an integer which defines the number of nucleotides in the oligonucleotide; wherein * represents a base pair between the nucleotides located on either side thereof; wherein each solid line represents a covalent bond between the nucleotides located on either side thereof; and wherein a represents an integer which defines a number of nucleotides with the proviso that a may be 0 or 1 and if 0, the A located 5′ of (X) a is bonded to the G located 3′ of (X) a.",
    "16. A compound having the formula: 3′ (X) n -(Seg. ID NO. 55)-P - (T/U) b - Q - (X) a -(Seg. ID NO. 52)-(X) n′ 5′ wherein each X represents a nucleotide which may be the same or different, P represents cytidylate or deoxycytidylate, Q represents guanvlate or deoxyguanylate and each or which may be substituted or modified in their sugar, base or phosphate; wherein each of A, C, G, U, and T represents a nucleotide which may be modified in its sugar, base or phosphate; wherein P - (T/U) b - Q represents P - (T) b - Q or P - (U) b - Q, with the proviso that b represents an integer which is 3, 4 or 5; wherein each of (X) n and (X) n′ represents an oligonucleotide having a predetermined sequence which is capable of hybridizing with an RNA target sequence; wherein each of n and n′ represents an integer which defines the number of nucleotides in the oligonucleotide such that (X) n and (X) n′ are sufficient to hybridize to the target sequence; wherein * represents a base pair between the nucleotides located on either side thereof; wherein each solid line represents a covalent bond between the nucleotides located on either side thereof; and wherein a represents an integer which defines a number of nucleotides with the proviso that a may be 0 or 1 and if 0, the A located 5′ of (X) a is bonded to the Q located 3′ of (X) a.",
    "17. The compound of claim 15 or 16, wherein the oligonucleotide 3′-(X) n - is 3′-(X) n−1 - A -.",
    "18. The compound of claim 15 or 16, wherein the oligonucleotide 3′-(X) n - is 3′-(X) n−2 - C - A -.",
    "19. The compound of claim 15 or 16, wherein (X) a is absent.",
    "20. The compound of claim 15 or 16, wherein the integer b of (T/U) b is equal to 3.",
    "21. The compound of claim 15 or 16, wherein the integer b of (T/U) b is equal to 4.",
    "22. The compound of claim 15, wherein each X is a deoxyribonucleotide.",
    "23. The compound of claim 16, wherein each X, P and Q is a deoxyribonucleotide.",
    "24. The compound of claim 16, wherein each X, P and Q is a ribonucleotide.",
    "25. The compound of claim 15; wherein b is equal to 3 or 4, each x ia a ribonucleotide, and C - (U) b - G is RNA.",
    "26. The compound of claim 15 or 16, wherein (T/U) b is a (T) b.",
    "27. The compound of claim 15 or 16, wherein (T/U) b is a (U) b.",
    "28. A composition which comprises a compound of claim 1, 4, 15, or 16 in association with an acceptable carrier.",
    "29. An oligonucleotide transfer vector containing a nucleotide sequence which on transcription gives rise to the compound of claim 1, 4, 15 or 16.",
    "30. The transfer vector of claim 29, wherein the transfer vector is a bacterial plasmid, a bacteriophage DNA, a cosmid, or an eukaryotic viral DNA.",
    "31. The oligonucleotide transfer vector of claim 29, wherein the oligonucleotide transfer vector is a plant DNA virus, a geminivirus or an infective phage particle.",
    "32. The oligonucleotide transfer vector of claim 29, wherein the oligonucleotide transfer vector is packaged and contains the promoter sequences for RNA polymerase II or RNA polymerase III.",
    "33. A host cell transformed by the transfer vector of claim 29.",
    "34. The host cell of claim 33, wherein the host cell is a prokaryotic host cell or an eukaryotic host cell.",
    "35. The prokaryotic host cell of claim 34, wherein the prokaryotic host cell is an E. coli host cell.",
    "36. The eukaryotic host cell of claim 34, wherein the eukaryotic host cell is a monkey COS host cell, a Chinese hamster ovary host cell, a mammalian host cell or a plant host cell.",
    "37. The compound of claim 1, 4, 15 or 16 which further comprises an antisense nucleic acid which is capable of hybridizing with an RNA target sequence.",
    "38. The compound of claim 1, 4, 15 or 16 which further comprises at least one additional non-naturally occurring oligonucleotide compound which comprises nucleotides whose sequence defines a conserved catalytic region and nucleotides whose sequence is capable of hybridizing with a predetermined target sequence.",
    "39. The compound of claim 38 wherein the additional non-naturally occurring oligonucleotide compound is a hammerhead ribozyme, a minizyme, a hairpin ribozyme, a hepatitis delta ribozyme, an RNAase P ribozyme or a combination thereof.",
    "40. The compound according to claim 15, comprising the formula: (Seq. ID NO. 37) wherein each of A, C, G, and U represents a ribonucleotide which may be modified in its sugar, base or phosphate; and wherein a represents a deoxyribonucleotide which may be modified in its sugar, base or phosphate.",
    "41. The compound according to claim 15, comprising the formula: (Seq. ID NO. 33) wherein each of A, C, G, and U represents a ribonucleotide which may be modified in its sugar, base or phosphate; and wherein each of a, c, g, and t represents a deoxyribonucleotide which may be modified in its sugar, base or phosphate.",
    "42. The compound according to claim 15, comprising the formula: (Seq. ID NO. 34) wherein each of A, C, G, and U represents a ribonucleotide which may be modified in its sugar, base or phosphate; and wherein each of a, c, g, and t represents a deoxyribonucleotide which may be modified in its sugar, base or phosphate.",
    "43. The compound according to claim 15, comprising the formula: (Seq. ID NO. 41) wherein each of A, C, G, and U represents a ribonucleotide which may be modified in its sugar, base or phosphate; and wherein each of a, c, g, and t represents a deoxyribonucleotide which may be modified in its sugar, base or phosphate.",
    "44. The compound according to claim 15, comprising the formula: (Seq. ID NO. 42) wherein each of A, C, G, and U represents a ribonucleotide which may be modified in its sugar, base or phosphate; and wherein each of a, c, g, and t represents a deoxyribonucleotide which may be modified in its sugar, base or phosphate.",
    "45. The compound according to claim 15, comprising the formula: (Seq. ID NO. 46) wherein each of A, C, G, and U represents a ribonucleotide which may be modified in its sugar, base or phosphate; and wherein each of a, c, g, and t represents a deoxyribonucleotide which may be modified in its sugar, base or phosphate.",
    "46. The compound according to claim 1, comprising the formula: (Seq. ID NO. 27) wherein each of A, C, G, and U represents a ribonucleotide which may be modified in its sugar, base or phosphate; and wherein each of a, c, g, and t represents a deoxyribonucleotide which may be modified in its sugar, base or phosphate. # SEQUENCE LISTING NUMBER OF SEQ ID NOS: 55 SEQ ID NO 1 LENGTH: 13 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 1 gcgggucaug aag # # # 13 SEQ ID NO 2 LENGTH: 42 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 2 gacacuucau cugaugaguc cuuuuggacg aaacccgcag gt # # 42 SEQ ID NO 3 LENGTH: 17 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (1) FEATURE: NAME/KEY: misc_RNA LOCATION: (6) FEATURE: NAME/KEY: misc_RNA LOCATION: (9) FEATURE: NAME/KEY: misc_RNA LOCATION: (17) SEQUENCE: 3 ncugangang uugaaan # # # 17 SEQ ID NO 4 LENGTH: 17 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (1) FEATURE: NAME/KEY: misc_RNA LOCATION: (6) FEATURE: NAME/KEY: misc_RNA LOCATION: (9) FEATURE: NAME/KEY: misc_RNA LOCATION: (17) SEQUENCE: 4 ncugangang ucgaaan # # # 17 SEQ ID NO 5 LENGTH: 29 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or #portion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (1)..(7) FEATURE: NAME/KEY: misc_RNA LOCATION: (25)..(29) SEQUENCE: 5 nnnnnnncug augagttttg aaacnnnnn # # 29 SEQ ID NO 6 LENGTH: 15 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 6 uccugucuug cauug # # # 15 SEQ ID NO 7 LENGTH: 29 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 7 caatgcaacu gaugagtttt gaaagagga # # 29 SEQ ID NO 8 LENGTH: 29 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 8 caatgcaacu gaugagtttt gaaacagga # # 29 SEQ ID NO 9 LENGTH: 28 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 9 caatgcaacu gacgaccttg aaacagga # # 28 SEQ ID NO 10 LENGTH: 25 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (16) SEQUENCE: 10 caatgcaacu gaugangaaa cagga # # 25 SEQ ID NO 11 LENGTH: 13 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 11 ggaagucagc cua # # # 13 SEQ ID NO 12 LENGTH: 35 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 12 gtcctaggct cugaugagtt ttgaaacttc ctgga # # 35 SEQ ID NO 13 LENGTH: 34 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 13 gtcctaggct cugaugattt tgaaacttcc tgga # # 34 SEQ ID NO 14 LENGTH: 17 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 14 uuccaugucg gcagaat # # # 17 SEQ ID NO 15 LENGTH: 31 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 15 attctgcccu gaugagtttt gaaacatgga a # # 31 SEQ ID NO 16 LENGTH: 30 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 16 attctgcccu gaugattttg aaacatggaa # # 30 SEQ ID NO 17 LENGTH: 31 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 17 attctgcccu gaugaggttt gaaacatgga a # # 31 SEQ ID NO 18 LENGTH: 20 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 18 ccaggcaguc agaucaucut # # # 20 SEQ ID NO 19 LENGTH: 34 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 19 aagatgatct cugaugagtt ttgaaactgc ctgg # # 34 SEQ ID NO 20 LENGTH: 33 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 20 aagatgatct cugaugattt tgaaactgcc tgg # # 33 SEQ ID NO 21 LENGTH: 17 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (1)..(17) SEQUENCE: 21 nnnnnnnnnn nnnnnnn # # # 17 SEQ ID NO 22 LENGTH: 17 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 22 attctgccga catggaa # # # 17 SEQ ID NO 23 LENGTH: 31 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 23 attctgcccu gaugagtttt gaaacatgga a # # 31 SEQ ID NO 24 LENGTH: 31 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 24 attctgcccu gaugagtttt gagacatgga a # # 31 SEQ ID NO 25 LENGTH: 15 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 25 uccugucuug cauug # # # 15 SEQ ID NO 26 LENGTH: 36 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 26 caatgcaacu gaugaguccu uuuggacgaa acagga # # 36 SEQ ID NO 27 LENGTH: 29 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 27 caatgcaacu gaugagtttt gaaacagga # # 29 SEQ ID NO 28 LENGTH: 29 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 28 caatgcaacu gaugagtttt gagacagga # # 29 SEQ ID NO 29 LENGTH: 15 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 29 caatgcaaga cagga # # # 15 SEQ ID NO 30 LENGTH: 15 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 30 acgaaagacg ctaag # # # 15 SEQ ID NO 31 LENGTH: 28 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 31 caatgcaacu gacgaccttg aaacagga # # 28 SEQ ID NO 32 LENGTH: 15 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 32 uccugucuug cauug # # # 15 SEQ ID NO 33 LENGTH: 29 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 33 caatgcaacu gaugagtttc gaaacagga # # 29 SEQ ID NO 34 LENGTH: 30 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 34 caatgcaacu gaugagtttt cgaaacagga # # 30 SEQ ID NO 35 LENGTH: 36 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 35 caatgcaacu gaugaguccu uuuggacgaa acagga # # 36 SEQ ID NO 36 LENGTH: 36 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 36 caatgcaacu gaugagtcct tttggacgaa acagga # # 36 SEQ ID NO 37 LENGTH: 30 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 37 caaugcaacu gaugaguuuu cgaaacagga # # 30 SEQ ID NO 38 LENGTH: 36 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 38 caaugcaacu gaugaguccu uuuggacgaa acagga # # 36 SEQ ID NO 39 LENGTH: 13 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 39 ggaagucagc cua # # # 13 SEQ ID NO 40 LENGTH: 20 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 40 uccaggaagu cagccuagga # # # 20 SEQ ID NO 41 LENGTH: 35 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 41 gtcctaggct cugaugagtt tcgaaacttc ctgga # # 35 SEQ ID NO 42 LENGTH: 36 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 42 gtcctaggct cugaugagtt ttcgaaactt cctgga # # 36 SEQ ID NO 43 LENGTH: 42 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 43 gtcctaggct cugaugagtc cttttggacg aaacttcctg ga # # 42 SEQ ID NO 44 LENGTH: 13 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 44 gcgaguccac act # # # 13 SEQ ID NO 45 LENGTH: 21 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 45 auuugcgagu ccacacugga g # # #21 SEQ ID NO 46 LENGTH: 36 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 46 ctccagtgtg cugaugagtt ttcgaaactc gcaaat # # 36 SEQ ID NO 47 LENGTH: 42 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Synthetic Ribozyme or por #tion thereof FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 47 ctccagtgtg cugaugagtc cttttggacg aaactcgcaa at # # 42 SEQ ID NO 48 LENGTH: 8 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (1) FEATURE: NAME/KEY: misc_RNA LOCATION: (6) SEQUENCE: 48 ncucanga # # # 8 SEQ ID NO 49 LENGTH: 5 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Combined D #NA/RNA Molecule: Synthetic Ribozyme or portion thereo #f FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (1) FEATURE: NAME/KEY: misc_RNA LOCATION: (5) SEQUENCE: 49 ngaan # # # 5 SEQ ID NO 50 LENGTH: 6 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Combined D #NA/RNA Molecule: Synthetic Ribozyme or portion thereo #f FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (1) FEATURE: NAME/KEY: misc_RNA LOCATION: (6) SEQUENCE: 50 ncgaan # # # 6 SEQ ID NO 51 LENGTH: 4 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Combined D #NA/RNA Molecule: Synthetic Ribozyme or portion thereo #f FEATURE: OTHER INFORMATION: n=t/u FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (1) SEQUENCE: 51 ngaa # # # 4 SEQ ID NO 52 LENGTH: 7 TYPE: RNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (5) SEQUENCE: 52 cuganga # # # 7 SEQ ID NO 53 LENGTH: 5 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Combined D #NA/RNA Molecule: Synthetic Ribozyme or portion thereo #f FEATURE: OTHER INFORMATION: n=t/u FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof FEATURE: NAME/KEY: misc_RNA LOCATION: (1) SEQUENCE: 53 ngaaa # # # 5 SEQ ID NO 54 LENGTH: 4 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Combined D #NA/RNA Molecule: Synthetic Ribozyme or portion thereo #f FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 54 cgaa # # # 4 SEQ ID NO 55 LENGTH: 3 TYPE: DNA ORGANISM: Artificial Sequence FEATURE: OTHER INFORMATION: Description of Combined D #NA/RNA Molecule: Synthetic Ribozyme or portion thereo #f FEATURE: OTHER INFORMATION: Description of Artificial #Sequence: Ribozymes and portions thereof SEQUENCE: 55 gaa # # # 3"
  ],
  "description_excerpt": "This application is a national stage application of PCT International Application No. PCT/AU96/00343, filed Jun. 7, 1996, which is a continuation of U.S. Ser. No. 08/574,396, filed Dec. 18, 1995 and now U.S. Pat. No. 6,001,648, which is a continuation-in-part of U.S. Ser. No. 08/488,181, filed Jun. 7, 1995 and now U.S. Pat. No. 6,004,806.\n\nThroughout this application various references are cited in bracket by author and publication year. The full citations are listed alphabetically and may be found immediately preceding the claims. These publications are hereby incorporated by reference into the present application.\n\nSeveral types of ribozymes have been identified in living organisms. One of the first ribozymes to show catalytic turnover was the RNA moiety of ribonuclease P. Ribonuclease P (RNase P) cleaves precursor tRNAs (pre-tRNAs) at their 5′ ends to give the mature 5′-termini of tRNAs. In Escherichia coli and Bacillus subtilis, the RNase P holoenzyme is composed of one basic protein subunit of approximate M r 14,000 (119 amino acids) and one single stranded RNA molecule of 377 and 401 nucleotides, respectively [Baer, 1990; Altman 1987; Waugh, 1989; Pace, 1990; Nichols, 1988]. Another early ribozyme to show cleavage was the L-19 intervening sequence (IVS) from tetrahymena. The 413 nucleotide intervening sequence (IVS) in the nuclear rRNA precursor from Tetrahymena thermophila can be excised and the two exons ligated in the complete absence of any protein [Kruger, 1982; Cech, 1981]. Unique to this class of self-splicing reaction is the requirement of a guanosine or 5′ guanosine nucleotide cofactor.",
  "cpc": [
    "C12N 15/113",
    "A61K 38/00",
    "C12N 2310/111",
    "C12N 2310/121",
    "C12N 2310/322"
  ],
  "ipc": [
    "A61K 31/70",
    "A61K 48/00",
    "C12N 1/21",
    "C12N 15/09",
    "C12N 15/113",
    "C12N 5/10",
    "C12N 9/00"
  ],
  "assignees": [
    "Commonwealth Scientific and Industrial Research Organization CSIRO"
  ],
  "inventors": [
    "Maxine J. McCall",
    "Philip Hendry",
    "Trevor Lockett"
  ],
  "filing_date": "1996-06-07",
  "publication_date": "2001-08-21",
  "grant_date": "2001-08-21",
  "priority_date": "1995-06-07",
  "application_number": "US-97356898-A",
  "family_id": "27049253",
  "cited_by_count": 73,
  "citations": [
    "US4511713A",
    "US5023243A",
    "WO1988004300A1",
    "US4987071A",
    "EP0321201A2",
    "WO1989005852A1",
    "AU5130190A",
    "WO1991003162A1",
    "US5149796A",
    "AU6218690A",
    "US5298612A"
  ]
}