US2009298787A1PendingUtilityA1

Dsrna as Insect Control Agent

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Assignee: DEVGEN NVPriority: Jan 12, 2006Filed: Jan 12, 2007Published: Dec 3, 2009
Est. expiryJan 12, 2026(expired)· nominal 20-yr term from priority
C12N 15/8282C12N 15/113A01N 57/16C12N 15/8285A01N 61/00C07K 14/43527Y02A40/146C07K 14/4354C12N 15/8286C12N 2310/14
50
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Claims

Abstract

The present invention relates to methods for controlling pest infestation using double standard RNA molecules. The invention provides methods for making transgenic plants that express the double stranded RNA molecules, as well as pesticidal agents and commodity products produced by the inventive plants.

Claims

exact text as granted — not AI-modified
1 . An isolated nucleotide sequence comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 49 to 158, 159, 160-163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 215, 220, 225, 230, 240 to 247, 249, 251, 253, 255, 257, 259, 275 to 472, 473, 478, 483, 488, 493, 498, 503, 508 to 513, 515, 517, 519, 521, 533 to 575, 576, 581, 586, 591, 596, 601, 603, 605, 607, 609, 621 to 767, 768, 773, 778, 783, 788, 793, 795, 797, 799, 801, 813 to 862, 863, 868, 873, 878, 883, 888, 890, 892, 894, 896, 908 to 1040, 1041, 1046, 1051, 1056, 1061, 1066 to 1071, 1073, 1075, 1077, 1079, 1081, 1083, 1085, 1087, 1089, 1091, 1093, 1095, 1097, 1099, 1101, 1103, 1105, 1107, 1109, 1111, 1113, 1161 to 1571, 1572, 1577, 1582, 1587, 1592, 1597, 1602, 1607, 1612, 1617, 1622, 1627, 1632, 1637, 1642, 1647, 1652, 1657, 1662, 1667, 1672, 1677, 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1730 to 2039, 2040, 2045, 2050, 2055, 2060, 2065, 2070, 2075, 2080, 2085, 2090, 2095, 2100, 2102, 2104, 2106, 2108, 2120 to 2338, 2339, 2344, 2349, 2354, 2359, 2364, 2366, 2368, 2370, 2372, 2384 to 2460, 2461, 2466, 2471, 2476, 2481 or 2486, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 49 to 158, 159, 160-163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 215, 220, 225, 230, 240 to 247, 249, 251, 253, 255, 257, 259, 275 to 472, 473, 478, 483, 488, 493, 498, 503, 508 to 513, 515, 517, 519, 521, 533 to 575, 576, 581, 586, 591, 596, 601, 603, 605, 607, 609, 621 to 767, 768, 773, 778, 783, 788, 793, 795, 797, 799, 801, 813 to 862, 863, 868, 873, 878, 883, 888, 890, 892, 894, 896, 908 to 1040, 1041, 1046, 1051, 1056, 1061, 1066 to 1071, 1073, 1075, 1077, 1079, 1081, 1083, 1085, 1087, 1089, 1091, 1093, 1095, 1097, 1099, 1101, 1103, 1105, 1107, 1109, 1111, 1113, 1161 to 1571, 1572, 1577, 1582, 1587, 1592, 1597, 1602, 1607, 1612, 1617, 1622, 1627, 1632, 1637, 1642, 1647, 1652, 1657, 1662, 1667, 1672, 1677, 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1730 to 2039, 2040, 2045, 2050, 2055, 2060, 2065, 2070, 2075, 2080, 2085, 2090, 2095, 2100, 2102, 2104, 2106, 2108, 2120 to 2338, 2339, 2344, 2349, 2354, 2359, 2364, 2366, 2368, 2370, 2372, 2384 to 2460, 2461, 2466, 2471, 2476, 2481 or 2486, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 49 to 158, 159, 160-163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 215, 220, 225, 230, 240 to 247, 249, 251, 253, 255, 257, 259, 275 to 472, 473, 478, 483, 488, 493, 498, 503, 508 to 513, 515, 517, 519, 521, 533 to 575, 576, 581, 586, 591, 596, 601, 603, 605, 607, 609, 621 to 767, 768, 773, 778, 783, 788, 793, 795, 797, 799, 801, 813 to 862, 863, 868, 873, 878, 883, 888, 890, 892, 894, 896, 908 to 1040, 1041, 1046, 1051, 1056, 1061, 1066 to 1071, 1073, 1075, 1077, 1079, 1081, 1083, 1085, 1087, 1089, 1091, 1093, 1095, 1097, 1099, 1101, 1103, 1105, 1107, 1109, 1111, 1113, 1161 to 1571, 1572, 1577, 1582, 1587, 1592, 1597, 1602, 1607, 1612, 1617, 1622, 1627, 1632, 1637, 1642, 1647, 1652, 1657, 1662, 1667, 1672, 1677, 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1730 to 2039, 2040, 2045, 2050, 2055, 2060, 2065, 2070, 2075, 2080, 2085, 2090, 2095, 2100, 2102, 2104, 2106, 2108, 2120 to 2338, 2339, 2344, 2349, 2354, 2359, 2364, 2366, 2368, 2370, 2372, 2384 to 2460, 2461, 2466, 2471, 2476, 2481 or 2486, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 49 to 158, 275 to 472, 533 to 575, 621 to 767, 813 to 862, 908 to 1040, 1161 to 1571, 1730 to 2039, 2120 to 2338, 2384 to 2460, or a complement thereof.   
     
     
         2 . A double stranded ribonucleotide sequence produced from the expression of a polynucleotide sequence of  claim 1 , wherein ingestion of said double stranded ribonucleotide sequence by a plant insect pest inhibits the growth of said insect pest. 
     
     
         3 . The double stranded ribonucleotide sequence of  claim 2 , wherein ingestion of said sequence inhibits expression of a nucleotide sequence substantially complementary to said sequence. 
     
     
         4 . A cell transformed with a polynucleotide comprising a nucleic acid sequence as defined in  claim 1 , optionally operably linked to a regulatory sequence. 
     
     
         5 . The cell of  claim 4 , wherein said cell is a plant cell. 
     
     
         6 . A plant transformed with a polynucleotide having a nucleic acid sequence as defined in  claim 1 , said nucleic acid sequence optionally operably linked to a regulatory sequence. 
     
     
         7 . The plant of  claim 6 , wherein said sequence inhibits a pest biological activity. 
     
     
         8 . The plant of  claim 6 , wherein said sequence inhibits expression of a target sequence. 
     
     
         9 . The plant of  claim 8  wherein said target sequence is an insect, nematode or fungal sequence. 
     
     
         10 . The plant of  claim 6 , wherein said plant is cytoplasmic male sterile. 
     
     
         11 . The plant of  claim 6 , wherein said plant further comprises or expresses a pesticidal agent selected from the group consisting of a patatin, a  Bacillus thuringiensis  insecticidal protein, a  Xenorhabdus  insecticidal protein, a  Photorhabdus  insecticidal protein, a  Bacillus laterosporous  insecticidal protein, and a  Bacillus sphearicus  insecticidal protein. 
     
     
         12 . The plant of  claim 11  wherein said  Bacillus thuringiensis  insecticidal protein is selected from the group consisting of a Cry1, a Cry3, a TIC851, a CryET170, a Cry22, a binary insecticidal protein CryET33 and CryET34, a binary insecticidal protein CryET80 and CryET76, a binary insecticidal protein TIC100 and TIC101, and a binary insecticidal protein PS149B1. 
     
     
         13 . The plant of  claim 6 , wherein said plant is chosen from the group comprising alfalfa, apple, apricot, artichoke, asparagus, avocado, banana, barley, beans, beet, blackberry, blueberry, broccoli, brussel sprouts, cabbage, canola, carrot, cassaya, cauliflower, a cereal, celery, cherry, citrus, clemintine, coffee, corn, cotton, cucumber, eggplant, endive, eucalyptus, figes, grape, grapefruit, groundnuts, ground cherry, kiwifruit, lettuce, leek, lemon, lime, pine, maize, mango, melon, millet, mushroom, nut aot, okra, onion, orange, an ornamental plant or flower or tree, papaya, parsley, pea, peach, peanut, peat, pepper, persimmon, pineapple, plantain, plum, pomegranate, potato, pumpkin, radicchio, radish, rapeseed, raspberry, rice, rye, sorghum, soy, soybean, spinach, strawberry, sugarbeet, sugarcane, sunflower, sweet potato, tangerine, tea, tobacco, tomato, a vine, watermelon, wheat, yams and zucchini. 
     
     
         14 . The plant of  claim 6 , wherein said plant is resistant against infestation by an insect chosen from the group comprising  Leptinotarsa  spp. (e.g.  L. decemlineata  (Colorado potato beetle),  L. juncta  (false potato beetle), or  L. texana  (Texan false potato beetle));  Lema  spp. (e.g.  L. trilineata  (three-lined potato beetle));  Epitrix  spp. (e.g.  E. cucumeris  (potato flea beetle),  E. hirtipennis  (flea beetle), or  E. tuberis  (tuber flea beetle));  Epicauta  spp. (e.g.  E. vittata  (striped blister beetle));  Epilachna  spp. (e.g.  E. varivetis  (mexican bean beetle));  Phaedon  spp. (e.g.  P. cochleariae  (mustard leaf beetle));  Nilaparvata  spp. (e.g.  N. lugens  (brown planthopper));  Laodelphax  spp. (e.g.  L. striatellus  (small brown planthopper));  Nephotettix  spp. (e.g.  N. virescens  or  N. cincticeps  (green leafhopper), or  N. nigropictus  (rice leafhopper));  Sogatella  spp. (e.g.  S. furcifera  (white-backed planthopper));  Acheta  spp. (e.g.  A. domesticus  (house cricket));  Blissus  spp. (e.g.  B. leucopterus leucopterus  (chinch bug));  Scotinophora  spp. (e.g.  S. vermidulate  (rice blackbug));  Acrosternum  spp. (e.g.  A. hilare  (green stink bug));  Parnara  spp. (e.g.  P. guttata  (rice skipper));  Chilo  spp. (e.g.  C. suppressalis  (rice striped stem borer),  C. auricilius  (gold-fringed stem borer), or  C. polychrysus  (dark-headed stem borer));  Chilotraea  spp. (e.g.  C. polychrysa  (rice stalk borer));  Sesamia  spp. (e.g.  S. inferens  (pink rice borer));  Tryporyza  spp. (e.g.  T. innotata  (white rice borer), or  T. incertulas  (yellow rice borer));  Cnaphalocrocis  spp. (e.g.  C. medinalis  (rice leafroller));  Agromyza  spp. (e.g.  A. oryzae  (leafminer), or  A. parvicornis  (corn blot leafminer));  Diatraea  spp. (e.g.  D. saccharalis  (sugarcane borer), or  D. grandiosella  (southwestern corn borer));  Narnaga  spp. (e.g.  N. aenescens  (green rice caterpillar));  Xanthodes  spp. (e.g.  X. transversa  (green caterpillar));  Spodoptera  spp. (e.g.  S. frugiperda  (fall armyworm),  S. exigua  (beet armyworm),  S. littoralis  (climbing cutworm), or  S. praefica  (western yellowstriped armyworm));  Mythimna  spp. (e.g.  Mythmna  ( Pseudaletia )  seperata  (armyworm));  Helicoverpa  spp. (e.g.  H. zea  (corn earworm));  Colaspis  spp. (e.g.  C. brunnea  (grape  colaspis ));  Lissorhoptrus  spp. (e.g.  L. oryzophilus  (rice water weevil));  Echinocnemus  spp. (e.g.  E. squamos  (rice plant weevil));  Diclodispa  spp. (e.g.  D. armigera  (rice hispa));  Oulema  spp. (e.g.  O. oryzae  (leaf beetle);  Sitophilus  spp. (e.g.  S. oryzae  (rice weevil));  Pachydiplosis  spp. (e.g.  P. oryzae  (rice gall midge));  Hydrellia  spp. (e.g.  H. griseola  (small rice leafminer), or  H. sasakii  (rice stem maggot));  Chlorops  spp. (e.g.  C. oryzae  (stem maggot));  Diabrotica  spp. (e.g.  D. virgifera virgifera  (western corn rootworm),  D. barberi  (northern corn rootworm),  D. undecimpunctata howardi  (southern corn rootworm),  D. virgifera zeae  (Mexican corn rootworm);  D. balteata  (banded cucumber beetle));  Ostrinia  spp. (e.g.  O. nubilalis  (European corn borer));  Agrotis  spp. (e.g.  A. ipsilon  (black cutworm));  Elasmopalpus  spp. (e.g.  E. lignosellus  (lesser cornstalk borer));  Melanotus  spp. (wireworms);  Cyclocephala  spp. (e.g.  C. borealis  (northern masked chafer), or  C. immaculata  (southern masked chafer));  Popillia  spp. (e.g.  P. japonica  (Japanese beetle));  Chaetocnema  spp. (e.g.  C. pulicaria  (corn flea beetle));  Sphenophorus  spp. (e.g.  S. maidis  (maize billbug));  Rhopalosiphum  spp. (e.g.  R. maidis  (corn leaf aphid));  Anuraphis  spp. (e.g.  A. maidiradicis  (corn root aphid));  Melanoplus  spp. (e.g.  M. femurrubrum  (redlegged grasshopper)  M. differentialis  (differential grasshopper) or  M. sanguinipes  (migratory grasshopper));  Hylemya  spp. (e.g.  H. platura  (seedcorn maggot));  Anaphothrips  spp. (e.g.  A. obscrurus  (grass thrips));  Solenopsis  spp. (e.g.  S. milesta  (thief ant)); or spp. (e.g.  T. urticae  (twospotted spider mite),  T. cinnabarinus  (carmine spider mite);  Helicoverpa  spp. (e.g.  H. zea  (cotton bollworm), or  H. armigera  (American bollworm));  Pectinophora  spp. (e.g.  P. gossypiella  (pink bollworm));  Earias  spp. (e.g.  E. vittella  (spotted bollworm));  Heliothis  spp. (e.g.  H. virescens  (tobacco budworm));  Anthonomus  spp. (e.g.  A. grandis  (boll weevil));  Pseudatomoscelis  spp. (e.g.  P. seriatus  (cotton fleahopper));  Trialeurodes  spp. (e.g.  T. abutiloneus  (banded-winged whitefly)  T. vaporariorum  (greenhouse whitefly));  Bemisia  spp. (e.g.  B. argentifolii  (silverleaf whitefly));  Aphis  spp. (e.g.  A. gossypii  (cotton aphid));  Lygus  spp. (e.g.  L. lineolaris  (tarnished plant bug) or  L. hesperus  (western tarnished plant bug));  Euschistus  spp. (e.g.  E. conspersus  (consperse stink bug));  Chlorochroa  spp. (e.g.  C. sayi  (Say stinkbug));  Nezara  spp. (e.g.  N. viridula  (southern green stinkbug));  Thrips  spp. (e.g.  T. tabaci  (onion thrips));  Frankliniella  spp. (e.g.  F. fusca  (tobacco thrips), or  F. occidentalis  (western flower thrips));  Empoasca  spp. (e.g.  E. fabae  (potato leafhopper));  Myzus  spp. (e.g.  M. persicae  (green peach aphid));  Paratrioza  spp. (e.g.  P. cockerelli  (psyllid));  Conoderus  spp. (e.g.  C. falli  (southern potato wireworm), or  C. vespertinus  (tobacco wireworm));  Phthorimaea  spp. (e.g.  P. operculella  (potato tuberworm));  Macrosiphum  spp. (e.g.  M. euphorbiae  (potato aphid));  Thyanta  spp. (e.g.  T. pallidovirens  (redshouldered stinkbug));  Phthorimaea  spp. (e.g.  P. operculella  (potato tuberworm));  Helicoverpa  spp. (e.g.  H. zea  (tomato fruitworm);  Keiferia  spp. (e.g.  K. lycopersicella  (tomato pinworm));  Limonius  spp. (wireworms);  Manduca  spp. (e.g.  M. sexta  (tobacco hornworm), or  M. quinquemaculata  (tomato hornworm));  Liriomyza  spp. (e.g.  L. sativae, L. trifolli  or  L. huidobrensis  (leafminer));  Drosophilla  spp. (e.g.  D. melanogaster, D. yakuba, D. pseudoobscura  or  D. simulans );  Carabus  spp. (e.g.  C. granulatus );  Chironomus  spp. (e.g.  C. tentanus );  Ctenocephalides  spp. (e.g.  C. felis  (cat flea));  Diaprepes  spp. (e.g.  D. abbreviatus  (root weevil));  Ips  spp. (e.g.  I. pini  (pine engraver));  Tribolium  spp. (e.g.  T. castaneum  (red floor beetle));  Glossina  spp. (e.g.  G. morsitans  (tsetse fly));  Anopheles  spp. (e.g.  A. gambiae  (malaria mosquito));  Helicoverpa  spp. (e.g.  H. armigera  (African Bollworm));  Acyrthosiphon  spp. (e.g.  A. pisum  (pea aphid));  Apis  spp. (e.g.  A. melifera  (honey bee));  Homalodisca  spp. (e.g.  H. coagulate  (glassy-winged sharpshooter));  Aedes  spp. (e.g.  Ae. aegypti  (yellow fever mosquito));  Bombyx  spp. (e.g.  B. mori  (silkworm));  Locusta  spp. (e.g.  L. migratoria  (migratory locust));  Boophilus  spp. (e.g.  B. microplus  (cattle tick));  Acanthoscurria  spp. (e.g.  A. gomesiana  (red-haired chololate bird eater));  Diploptera  spp. (e.g.  D. punctata  (pacific beetle cockroach));  Heliconius  spp. (e.g.  H. erato  (red passion flower butterfly) or  H. melpomene  (postman butterfly));  Curculio  spp. (e.g.  C. glandium  (acorn weevil));  Plutella  spp. (e.g.  P. xylostella  (diamondback moth));  Amblyomma  spp. (e.g.  A. variegatum  (cattle tick));  Anteraea  spp. (e.g.  A. yamamai  (silkmoth)); and  Armigeres  spp. (e.g.  A. subalbatus ). 
     
     
         15 . A seed or reproductive or propagation material for a plant of  claim 6 , wherein said seed or reproductive or propagation material comprises said polynucleotide or wherein said seed comprises a double stranded ribonucleotide sequence produced from the expression of said polynucleotide. 
     
     
         16 . A product produced from the plant of  claim 6 , wherein said product comprises said polynucleotide or a double stranded ribonucleotide sequence produced from the expression of said polynucleotide. 
     
     
         17 . The product of  claim 16 , wherein said product is selected from the group consisting of food, feed, fiber, paper, meal, protein, starch, flour, silage, coffee, tea, and oil. 
     
     
         18 . A pesticide comprising the product of  claim 16 , said product expressing said nucleic acid sequence. 
     
     
         19 . A method for controlling or preventing insect growth comprising providing an insect pest with the product of  claim 16 , wherein said product comprises a polynucleotide sequence that inhibits an insect biological activity. 
     
     
         20 . The method of  claim 19 , wherein said polynucleotide comprises said nucleic acid sequence as defined in  claim 1 . 
     
     
         21 . A method for producing a plant resistant against a plant pathogenic organism comprising:
 transforming a plant cell with a polynucleotide having a nucleic acid sequence as defined in  claim 1 , said nucleic acid sequence optionally operably linked to a regulatory sequence,   regenerating a plant from the transformed plant cell; and   growing the transformed plant under conditions suitable for the expression of an RNA molecule from said polynucleotide, said grown transformed plant resistant to said plant pathogenic organism compared to an untransformed plant.   
     
     
         22 . A method for improving yield, comprising:
 transforming a plant cell with a polynucleotide having a nucleic acid sequence as defined in  claim 1 , said nucleic acid sequence optionally operably linked to a regulatory sequence,   regenerating a plant from the transformed plant cell; and   growing the transformed plant under conditions suitable for the expression of an RNA molecule from said polynucleotide, said expression inhibiting feeding by a plant pathogenic organism and loss of yield due to pest infestation.   
     
     
         23 . The method according to  claim 50 , wherein polynucleotide expression produces an RNA molecule that suppresses a target gene in an insect pest that has ingested a portion of said crop plant, wherein said target gene performs at least one essential function selected from the group consisting of feeding by the pest, viability of the pest, pest cell apoptosis, differentiation and development of the pest or any pest cell, sexual reproduction by the pest, muscle formation, muscle twitching, muscle contraction, juvenile hormone formation and/or reduction, juvenile hormone regulation, ion regulation and transport, maintenance of cell membrane potential, amino acid biosynthesis, amino acid degradation, sperm formation, pheromone synthesis, pheromone sensing, antennae formation, wing formation, leg formation, egg formation, larval maturation, digestive enzyme formation, haemolymph synthesis, haemolymph maintenance, neurotransmission, larval stage transition, pupation, emergence from pupation, cell division, energy metabolism, respiration, cytoskeletal structure synthesis and maintenance, nucleotide metabolism, nitrogen metabolism, water use, water retention, and sensory perception. 
     
     
         24 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 49 to 158, 159, 160 to 163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 215, 220, 225, 230, 240 to 246, or 2486, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 49 to 158, 159, 160 to 163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 215, 220, 225, 230, 240 to 246, or 2486, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 49 to 158, 159, 160 to 163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 215, 220, 225, 230, 240 to 246, or 2486, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 49 to 158, or the complement thereof, and   the insect is chosen from the group comprising  Leptinotarsa  spp. (e.g.  L. decemlineata  (Colorado potato beetle),  L. juncta  (false potato beetle), and  L. texana  (Texan false potato beetle)).   
     
     
         25 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 247, 249, 251, 253, 255, 257, 259, 275 to 472, 473, 478, 483, 488, 493, 498, 503, 508 to 512, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 247, 249, 251, 253, 255, 257, 259, 275 to 472, 473, 478, 483, 488, 493, 498, 503, 508 to 512, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 247, 249, 251, 253, 255, 257, 259, 275 to 472, 473, 478, 483, 488, 493, 498, 503, 508 to 512, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 275 to 472, or the complement thereof, and   the insect is chosen from the group comprising  Phaedon  spp. (e.g.  P. cochleariae  (mustard leaf beetle)).   
     
     
         26 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 513, 515, 517, 519, 521, 533 to 575, 576, 581, 586, 591 or 596, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 513, 515, 517, 519, 521, 533 to 575, 576, 581, 586, 591 or 596, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 513, 515, 517, 519, 521, 533 to 575, 576, 581, 586, 591 or 596, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 533 to 575, or the complement thereof, and   the insect is chosen from the group comprising  Epilachna  spp. (e.g.  E. varivetis  (mexican bean beetle)).   
     
     
         27 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 601, 603, 605, 607, 609, 621 to 767, 768, 773, 778, 783 or 788, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 601, 603, 605, 607, 609, 621 to 767, 768, 773, 778, 783 or 788, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 601, 603, 605, 607, 609, 621 to 767, 768, 773, 778, 783 or 788, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 621 to 767, or the complement thereof, and   the insect is chosen from the group comprising  Anthonomus  spp. (e.g.  A. grandis  (boll weevil)).   
     
     
         28 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 793, 795, 797, 799, 801, 813 to 862, 863, 868, 873, 878 or 883, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 793, 795, 797, 799, 801, 813 to 862, 863, 868, 873, 878 or 883, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 793, 795, 797, 799, 801, 813 to 862, 863, 868, 873, 878 or 883, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 813 to 862, or the complement thereof, and   the insect is chosen from the group comprising  Tribolium  spp. (e.g.  T. castaneum  (red floor beetle)).   
     
     
         29 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 888, 890, 892, 894, 896, 908 to 1040, 1041, 1046, 1051, 1056, 1061, or 1066 to 1070, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 888, 890, 892, 894, 896, 908 to 1040, 1041, 1046, 1051, 1056, 1061, or 1066 to 1070, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 888, 890, 892, 894, 896, 908 to 1040, 1041, 1046, 1051, 1056, 1061, or 1066 to 1070, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 908 to 1040, or the complement thereof, and   the insect is chosen from the group comprising  Myzus  spp. (e.g.  M. persicae  (green peach aphid)).   
     
     
         30 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 1071, 1073, 1075, 1077, 1079, 1081, 1083, 1085, 1087, 1089, 1091, 1093, 1095, 1097, 1099, 1101, 1103, 1105, 1107, 1109, 1111, 1113, 1161 to 1571, 1572, 1577, 1582, 1587, 1592, 1597, 1602, 1607, 1612, 1617, 1622, 1627, 1632, 1637, 1642, 1647, 1652, 1657, 1662, 1667, 1672 or 1677, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 1071, 1073, 1075, 1077, 1079, 1081, 1083, 1085, 1087, 1089, 1091, 1093, 1095, 1097, 1099, 1101, 1103, 1105, 1107, 1109, 1111, 1113, 1161 to 1571, 1572, 1577, 1582, 1587, 1592, 1597, 1602, 1607, 1612, 1617, 1622, 1627, 1632, 1637, 1642, 1647, 1652, 1657, 1662, 1667, 1672 or 1677, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 1071, 1073, 1075, 1077, 1079, 1081, 1083, 1085, 1087, 1089, 1091, 1093, 1095, 1097, 1099, 1101, 1103, 1105, 1107, 1109, 1111, 1113, 1161 to 1571, 1572, 1577, 1582, 1587, 1592, 1597, 1602, 1607, 1612, 1617, 1622, 1627, 1632, 1637, 1642, 1647, 1652, 1657, 1662, 1667, 1672 or 1677, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 1161 to 1571, or the complement thereof, and   the insect is chosen from the group comprising  Nilaparvata  spp. (e.g.  N. lugens  (brown planthopper)).   
     
     
         31 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1730 to 2039, 2040, 2045, 2050, 2055, 2060, 2065, 2070, 2075, 2080, 2085, 2090 or 2095, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1730 to 2039, 2040, 2045, 2050, 2055, 2060, 2065, 2070, 2075, 2080, 2085, 2090 or 2095, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1730 to 2039, 2040, 2045, 2050, 2055, 2060, 2065, 2070, 2075, 2080, 2085, 2090 or 2095, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 1730 to 2039, or the complement thereof, and   the insect is chosen from the group comprising  Chilo  spp. (e.g.  C. suppressalis  (rice striped stem borer),  C. auricilius  (gold-fringed stem borer), or  C. polychysus  (dark-headed stem borer)).   
     
     
         32 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 2100, 2102, 2104, 2106, 2108, 2120 to 2338, 2339, 2344, 2349, 2354 or 2359, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 2100, 2102, 2104, 2106, 2108, 2120 to 2338, 2339, 2344, 2349, 2354 or 2359, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 2100, 2102, 2104, 2106, 2108, 2120 to 2338, 2339, 2344, 2349, 2354 or 2359, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 2120 to 2338, or the complement thereof, and   the insect is chosen from the group comprising  Plutella  spp. (e.g.  P. xylostella  (diamondback moth)).   
     
     
         33 . The method according to  claim 50  wherein:
 the nucleic acid sequence is chosen from the group comprising:   (i) sequences represented by any of SEQ ID NOs 2364, 2366, 2368, 2370, 2372, 2384 to 2460, 2461, 2466, 2471, 2476 or 2481, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 2364, 2366, 2368, 2370, 2372, 2384 to 2460, 2461, 2466, 2471, 2476 or 2481, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 2364, 2366, 2368, 2370, 2372, 2384 to 2460, 2461, 2466, 2471, 2476 or 2481, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 2384 to 2460, or the complement thereof, and   the insect is chosen from the group comprising  Acheta  spp. (e.g.  A. domesticus  (house cricket)).   
     
     
         34 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 49 to 158, 159, 160-163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 215, 220, 225, 230, 240 to 246, or 2486, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 49 to 158, 159, 160-163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 215, 220, 225, 230, 240 to 246, or 2486, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 49 to 158, 159, 160-163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 215, 220, 225, 230, 240 to 246, or 2486, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 49 to 158, or the complement thereof.   
     
     
         35 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 247, 249, 251, 253, 255, 257, 259, 275 to 472, 473, 478, 483, 488, 493, 498, 503, 508 to 512, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 247, 249, 251, 253, 255, 257, 259, 275 to 472, 473, 478, 483, 488, 493, 498, 503, 508 to 512, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 247, 249, 251, 253, 255, 257, 259, 275 to 472, 473, 478, 483, 488, 493, 498, 503, 508 to 512, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 275 to 472, or the complement thereof.   
     
     
         36 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 513, 515, 517, 519, 521, 533 to 575, 576, 581, 586, 591 or 596, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 513, 515, 517, 519, 521, 533 to 575, 576, 581, 586, 591 or 596, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 513, 515, 517, 519, 521, 533 to 575, 576, 581, 586, 591 or 596, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 533 to 575, or the complement thereof.   
     
     
         37 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 601, 603, 605, 607, 609, 621 to 767, 768, 773, 778, 783 or 788, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 601, 603, 605, 607, 609, 621 to 767, 768, 773, 778, 783 or 788, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 601, 603, 605, 607, 609, 621 to 767, 768, 773, 778, 783 or 788, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 621 to 767, or the complement thereof.   
     
     
         38 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 793, 795, 797, 799, 801, 813 to 862, 863, 868, 873, 878 or 883, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 793, 795, 797, 799, 801, 813 to 862, 863, 868, 873, 878 or 883, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 793, 795, 797, 799, 801, 813 to 862, 863, 868, 873, 878 or 883, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 813 to 862, or the complement thereof.   
     
     
         39 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 888, 890, 892, 894, 896, 908 to 1040, 1041, 1046, 1051, 1056, 1061, or 1066 to 1071, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 888, 890, 892, 894, 896, 908 to 1040, 1041, 1046, 1051, 1056, 1061, or 1066 to 1071, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 888, 890, 892, 894, 896, 908 to 1040, 1041, 1046, 1051, 1056, 1061, or 1066 to 1071, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 908 to 1040, or the complement thereof.   
     
     
         40 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 1071, 1073, 1075, 1077, 1079, 1081, 1083, 1085, 1087, 1089, 1091, 1093, 1095, 1097, 1099, 1101, 1103, 1105, 1107, 1109, 1111, 1113, 1161 to 1571, 1572, 1577, 1582, 1587, 1592, 1597, 1602, 1607, 1612, 1617, 1622, 1627, 1632, 1637, 1642, 1647, 1652, 1657, 1662, 1667, 1672 or 1677, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 1071, 1073, 1075, 1077, 1079, 1081, 1083, 1085, 1087, 1089, 1091, 1093, 1095, 1097, 1099, 1101, 1103, 1105, 1107, 1109, 1111, 1113, 1161 to 1571, 1572, 1577, 1582, 1587, 1592, 1597, 1602, 1607, 1612, 1617, 1622, 1627, 1632, 1637, 1642, 1647, 1652, 1657, 1662, 1667, 1672 or 1677, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 1071, 1073, 1075, 1077, 1079, 1081, 1083, 1085, 1087, 1089, 1091, 1093, 1095, 1097, 1099, 1101, 1103, 1105, 1107, 1109, 1111, 1113, 1161 to 1571, 1572, 1577, 1582, 1587, 1592, 1597, 1602, 1607, 1612, 1617, 1622, 1627, 1632, 1637, 1642, 1647, 1652, 1657, 1662, 1667, 1672 or 1677, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 1161 to 1571, or the complement thereof.   
     
     
         41 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1730 to 2039, 2040, 2045, 2050, 2055, 2060, 2065, 2070, 2075, 2080, 2085, 2090 or 2095, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1730 to 2039, 2040, 2045, 2050, 2055, 2060, 2065, 2070, 2075, 2080, 2085, 2090 or 2095, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1730 to 2039, 2040, 2045, 2050, 2055, 2060, 2065, 2070, 2075, 2080, 2085, 2090 or 2095, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 1730 to 2039, or the complement thereof.   
     
     
         42 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 2100, 2102, 2104, 2106, 2108, 2120 to 2338, 2339, 2344, 2349, 2354 or 2359, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 2100, 2102, 2104, 2106, 2108, 2120 to 2338, 2339, 2344, 2349, 2354 or 2359, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 2100, 2102, 2104, 2106, 2108, 2120 to 2338, 2339, 2344, 2349, 2354 or 2359, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 2120 to 2338, or the complement thereof.   
     
     
         43 . A transgenic plant resistant to an insect pest comprising a polynucleotide comprising a nucleic acid sequence selected from the group comprising:
 (i) sequences represented by any of SEQ ID NOs 2364, 2366, 2368, 2370, 2372, 2384 to 2460, 2461, 2466, 2471, 2476 or 2481, or the complement thereof,   (ii) sequences which are at least 70%, preferably at least 75%, 80%, 85%, 90%, more preferably at least 95%, 96%, 97%, 98% or 99% identical to a sequence represented by any of SEQ ID NOs 2364, 2366, 2368, 2370, 2372, 2384 to 2460, 2461, 2466, 2471, 2476 or 2481, or the complement thereof, and   (iii) sequences comprising at least 17 contiguous nucleotides of any of the sequences represented by SEQ ID NOs 2364, 2366, 2368, 2370, 2372, 2384 to 2460, 2461, 2466, 2471, 2476 or 2481, or the complement thereof,   or wherein said nucleic acid sequence is an orthologue of a gene comprising at least 17 contiguous nucleotides of any of SEQ ID NOs 2384 to 2460, or the complement thereof.   
     
     
         44 . The transgenic plant according to  claim 34  further comprising or expressing a pesticidal agent selected from the group consisting of a patatin, a  Bacillus thuringiensis  insecticidal protein, a  Xenorhabdus  insecticidal protein, a  Photorhabdus  insecticidal protein, a  Bacillus laterosporous  insecticidal protein, and a  Bacillus sphearicus  insecticidal protein. 
     
     
         45 . The transgenic plant of  claim 44  wherein said  Bacillus thuringiensis  insecticidal protein is selected from the group consisting of a Cry1, a Cry3, a TIC851, a CryET170, a Cry22, a binary insecticidal protein CryET33 and CryET34, a binary insecticidal protein CryET80 and CryET76, a binary insecticidal protein TIC100 and TIC101, and a binary insecticidal protein PS149B1. 
     
     
         46 - 48 . (canceled) 
     
     
         49 . A pesticide comprising a plant of  claim 6  or reproductive or propagation material thereof, said plant or reproductive or propagation material thereof expressing said nucleic acid sequence. 
     
     
         50 . A method for controlling or preventing insect growth comprising providing an insect pest with the plant of  claim 6  or reproductive or propagation material thereof, wherein said plant reproductive or propagation material thereof comprises a sequence that inhibits an insect biological activity. 
     
     
         51 . A method of  claim 50 , wherein said polynucleotide comprises said nucleic acid.

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