【技术实现步骤摘要】
【国外来华专利技术】
技术介绍
1、编码蛋白质lrrk2的富含亮氨酸的重复激酶2(lrrk2)基因位于染色体区域12q11.2-q13.1。lrrk2属于ras/gtp酶超家族的洛可蛋白家族。高度保守的lrrk2蛋白由51个外显子构成，总共2527个氨基酸，包括酶结构域，包含roc(复合物ras)gtp酶结构域和丝氨酸/苏氨酸激酶结构域。lrrk2蛋白中的其它蛋白相互作用结构域包含富含亮氨酸的重复结构域、c末端wd40重复结构域、犰狳蛋白和锚蛋白重复结构域。
2、lrrk2基因的突变被认为是显性遗传形式的帕金森氏病(parkinson's disease，pd)的病因，pd是一种逐渐衰弱的神经退行性综合征。lrrk2突变与额颞叶变性、皮质基底变性、黑质致密部(snpc)多巴胺能神经元变性、路易体(聚集α-突触核蛋白和其它泛素化蛋白的神经元内含物)的存在以及患者的相关运动神经元疾病的表型表现相关。在具有单核苷酸多态性(snp)的散发性pd病例中也发现了lrrk2突变，所述突变导致lrrk2表达增加(约2倍增加)，由于激酶活性增加，这可能与疾病的病...
【技术保护点】
1.一种用于抑制LRRK2的表达的双链核糖核酸(dsRNA)药剂，其中所述dsRNA药剂包括形成双链区的有义链和反义链，
2.一种用于抑制LRRK2的表达的双链核糖核酸(dsRNA)药剂，其中所述dsRNA药剂包括形成双链区的有义链和反义链，
3.一种用于抑制LRRK2的表达的双链核糖核酸(dsRNA)药剂，其中所述dsRNA药剂包括形成双链区的有义链和反义链，
4.根据权利要求1至3中任一项所述的dsRNA药剂，其中所述有义链包括与SEQ ID NO:1的核苷酸1458-1478、1484-1504、1761-1781、1950-...
【技术特征摘要】
【国外来华专利技术】
1.一种用于抑制lrrk2的表达的双链核糖核酸(dsrna)药剂，其中所述dsrna药剂包括形成双链区的有义链和反义链，
2.一种用于抑制lrrk2的表达的双链核糖核酸(dsrna)药剂，其中所述dsrna药剂包括形成双链区的有义链和反义链，
3.一种用于抑制lrrk2的表达的双链核糖核酸(dsrna)药剂，其中所述dsrna药剂包括形成双链区的有义链和反义链，
4.根据权利要求1至3中任一项所述的dsrna药剂，其中所述有义链包括与seq id no:1的核苷酸1458-1478、1484-1504、1761-1781、1950-1970、2076-2096、2094-2114、2212-2232、2213-2233、2268-2288、2431-2451、2529-2549、2565-2585、2566-2586、2569-2589、2583-2603、2605-2625、2657-2677、2764-2784、2867-2887、2881-2901、2883-2903、3022-3042、3198-3218、3330-3350、3348-3368、3395-3415、3629-3649、3630-3650、3712-3732、3713-3733、3715-3735、3717-3737、3720-3740、3727-3747、3796-3816、3800-3820、3822-3842、3829-3849、3875-3895、3971-3991、4130-4150、4443-4463、4447-4467、4449-4469、4478-4498、4488-4508、4619-4639、4652-4672、4868-4888、4950-4970、4970-4990、4971-4991、4972-4992、5092-5112、5202-5222、5226-5246、5232-5252、5233-5253、5273-5293、5318-5338、5367-5387、5368-5388、5370-5390、5373-5393、5425-5445、5443-5463、5457-5477、5461-5481、5471-5491、5475-5495、5501-5521、5557-5577、5640-5660、5646-5666、5659-5679、5674-5694、5675-5695、5676-5696、5682-5702、5684-5704、5722-5742、5725-5745、5778-5798、5779-5799、5793-5813、5964-5984、5965-5985、5984-6004、6029-6049、6092-6112、6093-6113、6094-6114、6096-6116、6127-6147、6143-6163、6165-6185、6172-6192、6173-6193、6174-6194、6175-6195、6198-6218、6319-6339,6339-6359,6418-6438,6531-6551,6536-6556,6541-6561,6573-6593,6662-6682,6730-6750,6740-6760,6742-6762,6786-6806,6791-6811,6803-6823,6804-6824,6805-6825,6807-6827,6810-6830,6811-6831,6812-6832,6818-6838,6872-6892,7004-7024,7018-7038,7020-7040,7027-7047,7028-7048,7085-7105,7103-7123,7115-7135,7121-7141,7127-7147,7242-7262,7348-7368,7397-7417,7404-7424,7405-7425,7421-7441,7443-7463,7444-7464,7445-7465,7493-7513,7535-7555,7538-7558,7539-7559,7593-7613,7629-7649,7637-7657,7638-7658,7639-7659,7671-7691,7727-7747,7729-7749,8134-8154,8135-8155,1484-1504,1488-1508,1755-1775,1761-1781,1905-1925,1945-1965,1950-1970,2029-2049,2207-2227,2212-2232,2213-2233,2431-2451,2529-2549,2565-2585,2569-2589,2648-2668,2764-2784,2874-2894,2881-2901,3051-3071,3193-3213,3198-3218,3208-3228,3330-3350,3331-3351,3350-3370,3380-3400,3390-3410,3395-3415,3573-3593,3622-3642,3632-3652,3712-3732,3715-3735,3717-3737,3718-3738,3740-3760,3795-3815,3806-3826,3829-3849,3830-3850,3938-3958,3950-3970,3971-3991,4367-4387,4376-4396,4444-4464,4446-4466,4447-4467,4551-4571,4554-4574,4704-4724,4834-4854,4839-4859,4925-4945,4970-4990,4971-4991,4972-4992,5058-5078,5092-5112,5128-5148,5196-5216,5226-5246,5275-5295,5322-5342,5349-5369,5352-5372,5365-5385,5367-5387,5368-5388,5370-5390,5373-5393,5461-5481,5475-5495,5482-5502,5515-5535,5516-5536,5541-5561,5557-5577,5607-5627,5635-5655,5641-5661,5643-5663,5644-5664,5646-5666,5655-5675,5659-5679,5660-5680,5671-5691,5674-5694,5682-5702,5683-5703,5684-5704,5721-5741,5757-5777,5763-5783,5772-5792,5773-5793,5776-5796,5777-5797,5778-5798,5779-5799,5793-5813,5794-5814,5964-5984,5965-5985,5966-5986,5980-6000,5984-6004,6029-6049,6030-6050,6071-6091,6092-6112,6093-6113,6095-6115,6129-6149,6135-6155,6136-6156,6142-6162,6145-6165,6171-6191,6172-6192,6174-6194,6175-6195,6178-6198,6180-6200,6196-6216,6197-6217,6198-6218,6344-6364,6355-6375,6520-6540,6536-6556,6538-6558,6539-6559,6541-6561,6723-6743,6724-6744,6729-6749,6730-6750,6737-6757,6740-6760,6742-6762,6743-6763,6786-6806,6787-6807,6791-6811,6793-6813,6794-6814,6803-6823,6805-6825,6806-6826,6807-6827,6808-6828,6810-6830,6811-6831,6812-6832,6813-6833,6814-6834,6818-6838,6828-6848,6829-6849,6834-6854,6872-6892,6918-6938,6919-6939,6920-6940,6922-6942,6989-7009,7004-7024,7012-7032,7023-7043,7035-7055,7036-7056,7041-7061,7085-7105,7103-7123,7114-7134,7116-7136,7121-7141,7129-7149,7146-7166,7149-7169,7242-7262,7247-7267,7303-7323,7348-7368,7353-7373,7397-7417,7404-7424,7405-7425,7443-7463,7493-7513,7533-7553,7538-7558,7539-7559,7593-7613,7627-7647,7629-7649,7727-7747,8005-8025,8007-8027和8134-8154的核苷酸序列中的任一个核苷酸序列相差不超过三个核苷酸的至少15个连续核苷酸，并且所述反义链包括来自seq id no:2的对应核苷酸序列的至少15个连续核苷酸。
5.根据权利要求1至4中任一项所述的dsrna药剂，其中所述反义链包括与选自由ad-1624152,ad-1624178,ad-1624412,ad-1624595,ad-1624721,ad-1624739,ad-1624856,ad-1624857,ad-1624894,ad-1625057,ad-1625155,ad-1625191,ad-1625192,ad-1625195,ad-1625209,ad-1625230,ad-1625282,ad-1625389,ad-1625485,ad-1625499,ad-1625501,ad-1625610,ad-1625786,ad-1625910,ad-1625928,ad-1625975,ad-1626183,ad-1626184,ad-1626265,ad-1626266,ad-1626268,ad-1626270,ad-1626273,ad-1626280,ad-1626349,ad-1626353,ad-1626375,ad-1626382,ad-1626428,ad-1626524,ad-1626636,ad-1626921,ad-1626925,ad-1626927,ad-1626936,ad-1626946,ad-1627077,ad-1627110,ad-1627308,ad-1627390,ad-1627410,ad-1627411,ad-1627412,ad-1627511,ad,1627601,ad-1627625,ad-1627631,ad-1627632,ad-1627672,ad-1627717,ad-1627766,ad-1627767,ad-1627769,ad-1627772,ad-1627820,ad-1627838,ad-1627852,ad-1627856,ad-1627866,ad-1627870,ad-1627896,ad-1627952,ad-1628008,ad-1628014,ad-1628027,ad-1628042,ad-1628043,ad-1628044,ad-1628050,ad-1628052,ad-1628070,ad-1628073,ad-1628118,ad-1628119,ad-1628133,ad-1628253,ad-1628254,ad-1628273,ad-1628318,ad-1628381,ad-1628382,ad-1628383,ad-1628385,ad-1628396,ad-1628412,ad-1628434,ad-1628441,ad-1628442,ad-1628443,ad-1628444,ad-1628467,ad-1628570,ad-1628590,ad-1628668,ad-1628754,ad-1628759,ad-1628764,ad-1628794,ad-1628883,ad-1628951,ad-1628961,ad-1628963,ad-1629007,ad-1629012,ad-1629024,ad-1629025,ad-1629026,ad-1629028,ad-1629031,ad-1629032,ad-1629033,ad-1629039,ad-1629092,ad-1629200,ad-1629214,ad-1629216,ad-1629223,ad-1629224,ad-1629263,ad-1629280,ad-1629292,ad-1629298,ad-1629304,ad-1629419,ad-1629524,ad-1629573,ad-1629580,ad-1629581,ad-1629597,ad-1629619,ad-1629620,ad-1629621,ad-1629665,ad-1629707,ad-1629710,ad-1629711,ad-1629763,ad-1629799,ad-1629807,ad-1629808,ad-1629809,ad-1629838,ad-1629876,ad-1629878,ad-1630135,ad-1630136,ad-1631019,ad-1631020,ad-1631021,ad-1631022,ad-1631023,ad-1631024,ad-1631025,ad-1631026,ad-1631027,ad-1631028,ad-1631029,ad-1631030,ad-1631031,ad-1631032,ad-1631033,ad-1631034,ad-1631035,ad-1631036,ad-1631037,ad-1631038,ad-1631039,ad-1631040,ad-1631041,ad-1631042,ad-1631043,ad-1631044,ad-1631045,ad-1631046,ad-1631047,ad-1631048,ad-1631049,ad-1631050,ad-1631051,ad-1631052,ad-1631053,ad-1631054,ad-1631055,ad-1631056,ad-1631057,ad-1631058,ad-1631059,ad-1631060,ad-1631061,ad-1631062,ad-1631063,ad-1631064,ad-1631065,ad-1631066,ad-1631067,ad-1631068,ad-1631069,ad-1631070,ad-1631071,ad-1631072,ad-1631073,ad-1631074,ad-1631075,ad-1631076,ad-1631077,ad-1631078,ad-1631079,ad-1631080,ad-1631081,ad-1631082,ad-1631083,ad-1631084,ad-1631085,ad-1631086,ad-1631087,ad-1631088,ad-1631089,ad-1631090,ad-1631091,ad-1631092,ad-1631093,ad-1631094,ad-1631095,ad-1631096,ad-1631097,ad-1631098,ad-1631099,ad-1631100,ad-1631101,ad-1631102,ad-1631103,ad-1631104,ad-1631105,ad-1631106,ad-1631107,ad-1631108,ad-1631109,ad-1631110,ad-1631111,ad-1631112,ad-1631113,ad-1631114,ad-1631115,ad-1631116,ad-1631117,ad-1631118,ad-1631119,ad-1631120,ad-1631121,ad-1631122,ad-1631123,ad-1631124,ad-1631125,ad-1631126,ad-1631127,ad-1631128,ad-1631129,ad-1631130,ad-1631131,ad-1631132,ad-1631133,ad-1631134,ad-1631135,ad-1631136,ad-1631137,ad-1631138,ad-1631139,ad-1631140,ad-1631141,ad-1631142,ad-1631143,ad-1631144,ad-1631145,ad-1631146,ad-1631147,ad-1631148,ad-1631149,ad-1631150,ad-1631151,ad-1631152,ad-1631153,ad-1631154,ad-1631155,ad-1631156,ad-1631157,ad-1631158,ad-1631159,ad-1631160,ad-1631161,ad-1631162,ad-1631163,ad-1631164,ad-1631165,ad-1631166,ad-1631167,ad-1631168,ad-1631169,ad-1631170,ad-1631171,ad-1631172,ad-1631173,ad-1631174,ad-1631175,ad-1631176,ad-1631177,ad-1631178,ad-1631179,ad-1631180,ad-1631181,ad-1631182,ad-1631183,ad-1631184,ad-1631185,ad-1631186,ad-1631187,ad-1631188,ad-1631189,ad-1631190,ad-1631191,ad-1631192,ad-1631193,ad-1631194,ad-1631195,ad-1631196,ad-1631197,ad-1631198,ad-1631199,ad-1631200,ad-1631201,ad-1631202,ad-1631203,ad-1631204,ad-1631205,ad-1631206,ad-1631207,ad-1631208,ad-1631209,ad-1631210,ad-1631211,ad-1631212,ad-1631213,ad-1631214,ad-1631215,ad-1631216,ad-1631217,ad-1631218,ad-1631219,ad-1631220,ad-1631221,ad-1807334,ad-1807335,ad-1807336,ad-1807337,ad-1807338,ad-1807339,ad-1807340,ad-1807341,ad-1807342,ad-1807343,ad-1807344,ad-1807345,ad-1807346,ad-1807347,ad-1807348,ad-1807349,ad-1807350,ad-1807351,ad-1807352,ad-1807353,ad-1807354,ad-1807355,ad-1807356,ad-1807357,ad-1807358,ad-1807359,ad-1807360,ad-1807361,ad-1807362,ad-1807363,ad-1807364,ad-1807365,ad-1807366,ad-1807367,ad-1807368,ad-1807369,ad-1807370,ad-1807371,ad-1807372,ad-1807373,ad-1807374,ad-1807375,ad-1807376,ad-1807377,ad-1807378,ad-1807379,ad-1807380,ad-1807381,ad-1807382,ad-1807383,ad-1807384,ad-1807385,ad-1807386,ad-1807387,ad-1807388,ad-1807389,ad-1807390,ad-1807391,ad-1807392,ad-1807393,ad-1807394,ad-1807395,ad-1807396,ad-1807397,ad-1807398,ad-1807399,ad-1807400,ad-1807401,ad-1807402,ad-1807403,ad-1807404,ad-1807405,ad-1807406,ad-1807407,ad-1807408,ad-1807409,ad-1807410,ad-1807411,ad-1807412,ad-1807413,ad-1807414,ad-1807415,ad-1807416,ad-1807417,ad-1807418,ad-1807419,ad-1807420,ad-1807421,ad-1807422和ad-1807423组成的组的双链体的反义链核苷酸序列中的任一个反义链核苷酸序列相差不超过三个核苷酸的至少15个连续核苷酸。
6.根据权利要求2至3中任一项所述的dsrna药剂，其中所述有义链包括与seq id no:1808的核苷酸212-232,238-258,515-535,704-724,830-850,848-868,966-986,967-987,1022-1042,1185-1205,1283-1303,1319-1339,1320-1340,1323-1343,1337-1357,1359-1379,1411-1431,1518-1538,1621-1641,1635-1655,1637-1657,1776-1796,1952-1972,2084-2104,2102-2122,2149-2169,2383-2403,2384-2404,2466-2486,2467-2487,2469-2489,2471-2491,2474-2494,2481-2501,2550-2570,2554-2574,2576-2596,2583-2603,2629-2649,2725-2745,2884-2904,3197-3217,3201-3221,3203-3223,3232-3252,3242-3262,3373-3393,3406-3426,3622-3642,3704-3724,3724-3744,3725-3745,3726-3746,3846-3866,3956-3976,3980-4000,3986-4006,3987-4007,4027-4047,4072-4092,4121-4141,4122-4142,4124-4144,4127-4147,4179-4199,4197-4217,4211-4231,4215-4235,4225-4245,4229-4249,4255-4275,4311-4331,4394-4414,4400-4420,4413-4433,4428-4448,4429-4449,4430-4450,4436-4456,4438-4458,4476-4496,4479-4499,4532-4552,4533-4553,4547-4567,4718-4738,4719-4739,4738-4758,4783-4803,4846-4866,4847-4867,4848-4868,4850-4870,4881-4901,4897-4917,4919-4939,4926-4946,4927-4947,4928-4948,4929-4949,4952-4972,5073-5093,5093-5113,5172-5192,5285-5305,5290-5310,5295-5315,5327-5347,5416-5436,5484-5504,5494-5514,5496-5516,5540-5560,5545-5565,5557-5577,5558-5578,5559-5579,5561-5581,5564-5584,5565-5585,5566-5586,5572-5592,5626-5646,5758-5778,5772-5792,5774-5794,5781-5801,5782-5802,5839-5859,5857-5877,5869-5889,5875-5895,5881-5901,5996-6016,6102-6122,6151-6171,6158-6178,6159-6179,6175-6195,6197-6217,6198-6218,6199-6219,6247-6267,6289-6309,6292-6312,6293-6313,6347-6367,6383-6403,6391-6411,6392-6412,6393-6413,6425-6445,6481-6501,6483-6503,6888-6908和6889-6909的核苷酸序列中的任一个核苷酸序列相差不超过三个核苷酸的至少15个连续核苷酸，并且所述反义链包括来自seqid no:1809的对应核苷酸序列的至少15个连续核苷酸。
7.根据权利要求2至3或6中任一项所述的dsrna药剂，其中所述反义链包括与选自由ad-1624152,ad-1624178,ad-1624412,ad-1624595,ad-1624721,ad-1624739,ad-1624856,ad-1624857,ad-1624894,ad-1625057,ad-1625155,ad-1625191,ad-1625192,ad-1625195,ad-1625209,ad-1625230,ad-1625282,ad-1625389,ad-1625485,ad-1625499,ad-1625501,ad-1625610,ad-1625786,ad-1625910,ad-1625928,ad-1625975,ad-1626183,ad-1626184,ad-1626265,ad-1626266,ad-1626268,ad-1626270,ad-1626273,ad-1626280,ad-1626349,ad-1626353,ad-1626375,ad-1626382,ad-1626428,ad-1626524,ad-1626636,ad-1626921,ad-1626925,...
【专利技术属性】
技术研发人员：L·T·H·党，J·D·麦金因克，M·K·施莱格尔，A·卡斯托雷诺，T·M·阮，J·巴里，M·斯特里科斯，S·勒布朗克，
申请(专利权)人：阿尔尼拉姆医药品有限公司，
类型：发明
国别省市：
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