Nanoparticle type oligonucleotide structure having high efficiency and method for preparing same

    公开(公告)号:US10030243B2

    公开(公告)日:2018-07-24

    申请号:US14902563

    申请日:2014-07-04

    摘要: The present invention relates to an oligonucleotide structure and a method for preparing the same and, more particularly, to an oligonucleotide structure in which a polymer compound is linked to an oligonucleotide via a covalent bond to improve in vivo stability of the oligonucleotide and cellular delivery efficiency of the oligonucleotide; and to a method for preparing the same. The oligonucleotide structure is improved into a homogenous material, thereby solving the problem in material verification due to polydispersion characteristics occurring when a hydrophilic material linked to the oligonucleotide is a synthetic polymer; the oligonucleotide structure is easy to synthesize compared with the existing process; and the size of a double-stranded oligo RNA structure can be accurately adjusted through the control of the repetition number of a hydrophilic material block, and thus, the gene expression regulation function of the oligonucleotide does not deteriorate through the synthesis of the optimized oligonucleotide structure, and the oligonucleotide can be delivered into cells at even a relatively low-concentration dosage. Therefore, the oligonucleotide structure of the present invention can be useful as a novel type oligonucleotide delivery system as well as a tool for treating cancers, infectious diseases, and the like.

    METHOD OF MANUFACTURING MICRO CHAMBER PLATE WITH BUILT-IN SAMPLE AND ANALYTIC MICRO CHAMBER PLATE, ANALYTIC MICRO CHAMBER PLATE AND APPARATUS SET FOR MANUFACTURING ANALYTIC MICRO CHAMBER PLATE WITH BUILT-IN SAMPLE
    64.
    发明申请
    METHOD OF MANUFACTURING MICRO CHAMBER PLATE WITH BUILT-IN SAMPLE AND ANALYTIC MICRO CHAMBER PLATE, ANALYTIC MICRO CHAMBER PLATE AND APPARATUS SET FOR MANUFACTURING ANALYTIC MICRO CHAMBER PLATE WITH BUILT-IN SAMPLE 有权
    使用内置样品和分析微孔板制造微型板的方法,分析型微孔板和用于制造具有内置样品的分析微室板的装置

    公开(公告)号:US20160023205A1

    公开(公告)日:2016-01-28

    申请号:US14875246

    申请日:2015-10-05

    IPC分类号: B01L3/00

    摘要: A method of manufacturing a micro-chamber plate with a built-in sample, including: settling a micro-chamber plate for sample injection at a micro-chamber plate receiving part formed with an upper opening; disposing a cover for micro-chamber plate receiving part to cover the upper opening, the cover for micro-chamber plate receiving part having a provisional storing part and an auxiliary covering part connected with the provisional storing part and formed with a through-hole for auxiliary covering part; and manufacturing a micro-chamber plate with a built-in sample by putting the micro-chamber plate receiving part, on which the cover is disposed, into a centrifugal separator which can apply vacuum, applying centrifugal force and injecting a sample solution provisionally stored in the provisional storing part into the micro-chamber plate through a vessel communication part which is formed at the provisional storing part to be communicated with the micro-chamber plate receiving part.

    摘要翻译: 一种制造具有内置样品的微室板的方法,包括:在形成有上部开口的微室板接收部分处沉积用于样品注入的微室板; 设置用于微室板接收部分的盖以覆盖上开口,用于具有临时存储部分的微室板接收部分的盖和与临时存储部分连接的辅助覆盖部分,并形成有用于辅助的通孔 覆盖部分; 并通过将其上设置有盖的微室板接收部分放置在可以施加真空的离心分离器中,通过施加离心力并将临时存储的样品溶液注入到其中来制造具有内置样品的微室板 临时存储部分通过形成在临时存储部分处以与微室板接收部分连通的容器连通部分进入微室板。

    AMPHIREGULIN-SPECIFIC DOUBLE-HELICAL OLIGO-RNA, DOUBLE-HELICAL OLIGO-RNA STRUCTURE COMPRISING DOUBLE-HELICAL OLIGO-RNA, AND COMPOSITION FOR PREVENTING OR TREATING RESPIRATORY DISEASES CONTAINING SAME
    65.
    发明申请
    AMPHIREGULIN-SPECIFIC DOUBLE-HELICAL OLIGO-RNA, DOUBLE-HELICAL OLIGO-RNA STRUCTURE COMPRISING DOUBLE-HELICAL OLIGO-RNA, AND COMPOSITION FOR PREVENTING OR TREATING RESPIRATORY DISEASES CONTAINING SAME 审中-公开
    AMPHIREGULIN特异性双螺旋OLIGO-RNA,包含双重OLILO-RNA的双重HOLIC OLIGO-RNA结构,以及用于预防或治疗含有它的呼吸道疾病的组合物

    公开(公告)号:US20150259690A1

    公开(公告)日:2015-09-17

    申请号:US14433627

    申请日:2013-10-07

    摘要: An amphiregulin-specific double-stranded oligo siRNA structure comprises hydrophilic and hydrophobic compounds bound to the amphiregulin-specific double-stranded oligo siRNA by a simple covalent bond or a linker-mediated covalent bond so as to increase the in vivo stability and intracellular delivery efficiency of the double-stranded oligo siRNA, and to nanoparticles composed of the oligo siRNA structures. The amphiregulin-specific double-stranded oligo siRNA structure can increase the stability of the amphiregulin-specific double-stranded oligo siRNA without impairing the function of the amphiregulin-specific double-stranded oligo siRNA, and at the same time, can efficiently increase the membrane permeability of the double-stranded oligo siRNA. Thus, when the amphiregulin-specific double-stranded oligo siRNA structure is used, the amphiregulin-specific double-stranded oligo siRNA can be efficiently delivered into cells even when it is administered at a relatively low concentration, so that it can be effectively used for the prevention or treatment of respiratory diseases.

    摘要翻译: 双调蛋白特异性双链寡核苷酸siRNA结构包含通过简单的共价键或连接体介导的共价键与双调蛋白特异性双链寡核苷酸结合的亲水和疏水化合物,以增加体内稳定性和细胞内递送效率 的双链寡聚siRNA,以及由寡聚siRNA结构构成的纳米颗粒。 双调蛋白特异性双链寡聚siRNA结构可以增加双调蛋白特异性双链寡聚siRNA的稳定性,而不损害双调蛋白特异性双链寡聚siRNA的功能,同时可以有效地增加膜 双链寡聚siRNA的通透性。 因此,当使用双调蛋白特异性双链寡聚siRNA结构时,即使以相对低的浓度给药,也可以将双调蛋白特异性双链寡聚siRNA有效地递送到细胞中,使得其可以有效地用于 预防或治疗呼吸系统疾病。

    HIGH-SENSITIVITY NUCLEIC ACID PREPARATION METHODS FOR THE DETECTION OF NUCLEIC ACID BY NUCLEIC ACID POLYMERASE
    66.
    发明申请
    HIGH-SENSITIVITY NUCLEIC ACID PREPARATION METHODS FOR THE DETECTION OF NUCLEIC ACID BY NUCLEIC ACID POLYMERASE 审中-公开
    用于通过核酸聚合酶检测核酸的高灵敏度核酸制备方法

    公开(公告)号:US20150072351A1

    公开(公告)日:2015-03-12

    申请号:US14391155

    申请日:2013-04-08

    IPC分类号: C12Q1/68 C12N15/10

    摘要: The present invention relates to a method for preparing a nucleic acid with high sensitivity, wherein a nucleic acid polymerase is used to add a terminator to the nucleic acid to be used for analysis prior to a nucleic acid polymerization reaction such as a PCR reaction, a real time quantitative PCR reaction, or the like, for detecting a trace of nucleic acid, such that a non-specific priming occurring competitively with an amplification reaction of a target nucleic acid may be basically eliminated, thereby precisely detecting only the trace of target nucleic acid and precisely measuring a concentration of the target nucleic acid.

    摘要翻译: 本发明涉及一种制备具有高灵敏度的核酸的方法,其中使用核酸聚合酶将核酸聚合反应如PCR反应之前用于分析的核酸加入终止子, 实时定量PCR反应等,用于检测核酸的痕迹,使得可以基本上消除与目标核酸的扩增反应竞争性发生的非特异性引发,从而精确检测目标核酸的痕迹 酸并精确测量靶核酸的浓度。

    COMPOSITION FOR HOT-START REVERSE TRANSCRIPTION REACTION OR HOT-START REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION
    67.
    发明申请
    COMPOSITION FOR HOT-START REVERSE TRANSCRIPTION REACTION OR HOT-START REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION 审中-公开
    反应转录反应或反应快速反应转化聚合酶链反应的组合物

    公开(公告)号:US20150044683A1

    公开(公告)日:2015-02-12

    申请号:US14383793

    申请日:2013-03-11

    IPC分类号: C12Q1/68 C12P19/34

    摘要: A composition for hot-start reverse transcription reaction and a composition for reverse transcription PCR are disclosed. The composition is obtained by adding pyrophosphate and pyrophosphatase to an aqueous solution containing reaction buffer solution, MgCl2, four kinds of dNTPs, and reverse transcription polymerase in a single reaction tube. The composition for hot-start reverse transcription reaction is obtained by freezing or drying the composition. The composition show increased stability and long-term storage stability. Also, disclosed is a composition that additionally includes DNA polymerase, and, thus, enables a hot-start reverse transcription reaction and a PCR reaction to be sequentially performed. A method for amplifying a nucleic acid by using the composition. The composition of the invention can be conveniently and effectively used in multiplex reverse transcription PCRs or real-time quantitative reverse transcription PCR.

    摘要翻译: 公开了一种用于热启动逆转录反应的组合物和用于逆转录PCR的组合物。 通过在单个反应管中将焦磷酸盐和焦磷酸酶加入到含有反应缓冲液,MgCl 2,四种dNTP和逆转录聚合酶的水溶液中来获得组合物。 通过冷冻或干燥组合物获得热启动逆转录反应的组合物。 该组合物显示出增加的稳定性和长期储存稳定性。 此外,公开了另外包含DN​​A聚合酶的组合物,因此能够依次进行热启动逆转录反应和PCR反应。 一种通过使用该组合物来扩增核酸的方法。 本发明的组合物可以方便有效地用于多重逆转录PCR或实时定量逆转录PCR。

    APPARATUS AND METHOD FOR AUTOMATICALLY ANALYZING BIOLOGICAL SAMPLES
    68.
    发明申请
    APPARATUS AND METHOD FOR AUTOMATICALLY ANALYZING BIOLOGICAL SAMPLES 有权
    用于自动分析生物样品的装置和方法

    公开(公告)号:US20150037803A1

    公开(公告)日:2015-02-05

    申请号:US14377537

    申请日:2013-02-07

    IPC分类号: C12Q1/68

    摘要: Provided are an apparatus and a method for automatically analyzing biological samples capable of performing the entire processes of dissolving the biological samples in protease and cell lysate to dissolve a nucleic acid in a solution, attaching the nucleic acid to magnetic particles, finally washing the magnetic particle to which the nucleic acid is attached with an organic solvent, drying the magnetic particles using a vacuum pump, eluting the target nucleic acid attached to the magnetic particles in an aqueous solution, adding and mixing the eluted target nucleic acid into a vessel containing a nucleic acid amplification reagent, real-time detecting amplification by irradiating excitation light to a reactor simultaneously with regulating a temperature to perform amplification to measure fluorescence, inactivating an amplified product using an ultraviolet lamp after amplification, obtaining an image through electrophoresis, and analyzing a molecular weight in a single apparatus.

    摘要翻译: 提供了一种用于自动分析生物样品的装置和方法,其能够执行将生物样品溶解在蛋白酶和细胞裂解物中的整个过程,以将核酸溶解在溶液中,将核酸附着到磁性颗粒上,最后洗涤磁性颗粒 核酸与有机溶剂连接在其上,使用真空泵干燥磁性颗粒,用水溶液洗脱附着在磁性颗粒上的靶核酸,加入并将洗脱的目标核酸混合到含有核酸的容器中 酸扩增试剂,通过在调节温度的同时照射激发光同时进行扩增以测量荧光,扩增后的紫外线灯灭活扩增产物,通过电泳获得图像,分析分子量,实时检测扩增 在一个单一的设备。

    HIGH-EFFICIENCY NANOPARTICLE-TYPE DOUBLE-HELICAL OLIGO-RNA STRUCTURE AND METHOD FOR PREPARING SAME
    69.
    发明申请
    HIGH-EFFICIENCY NANOPARTICLE-TYPE DOUBLE-HELICAL OLIGO-RNA STRUCTURE AND METHOD FOR PREPARING SAME 有权
    高效纳米二型双螺旋OLIGO-RNA结构及其制备方法

    公开(公告)号:US20150005364A1

    公开(公告)日:2015-01-01

    申请号:US14370035

    申请日:2013-01-04

    IPC分类号: A61K9/14 C12N15/113

    摘要: Provided are a double-stranded oligo RNA structure and a method of preparing the same, and more specifically, a double-stranded oligo RNA structure in which a polymer compound is covalently bound to a double-stranded oligo RNA in order to improve stability in vivo and a cell delivery efficiency of the double-stranded oligo RNA, and a method of preparing the same.The double-stranded oligo RNA structure having the optimized structure according to the present invention may not inhibit functions of the double-stranded oligo RNA, but effectively improve stability and cell membrane permeability of the double-stranded oligo RNA, such that the double-stranded oligo RNA may be delivered into the cell even at a low concentration dosage thereof to be significantly used as a tool for treatment of cancer, infectious diseases, and the like, as well as a new delivery system of the double-stranded oligo RNA.

    摘要翻译: 提供双链寡聚RNA结构及其制备方法,更具体地,其中高分子化合物与双链寡RNA共价结合以提高体内稳定性的双链寡聚RNA结构 和双链寡聚RNA的细胞递送效率及其制备方法。 具有本发明优化结构的双链寡聚RNA结构可能不抑制双链寡聚RNA的功能,而且可有效提高双链寡RNA的稳定性和细胞膜通透性,使得双链寡聚RNA 寡核苷酸即使以低浓度剂量也可以递送到细胞中,以显着地用作治疗癌症,感染性疾病等的工具,以及双链寡聚RNA的新的递送系统。