DNA DAMAGE DEPENDENT MICRORNA SIGNATURE FOR CANCERS, METHODS AND USES RELATED THERETO

    公开(公告)号:US20230407401A1

    公开(公告)日:2023-12-21

    申请号:US17998888

    申请日:2020-09-04

    发明人: Sagar SENGUPTA

    IPC分类号: C12Q1/6886 C12N15/113

    摘要: The present invention related to microRNA (miR) signatures also called DNA damage sensitive miRs (DDSMs) which responds to the levels of DNA damage. The present invention provides method for identification of DDSMs which are upregulated by a common transcription factor (CDX2). Further, the present invention also provides miR inhibitors along with nanoparticle or hydrogel or adenoviral based delivery system for administering the same and kits comprising the same. The microRNA (miR) signature of the present invention can be used as biological markers to detect earliest stages of cancers particularly colon cancers. The present invention also provides a method of treatment of other types of cancer and related diseases.

    RAPID METHOD FOR GENERATING GENE KNOCK DOWN MODEL
    6.
    发明申请
    RAPID METHOD FOR GENERATING GENE KNOCK DOWN MODEL 审中-公开
    用于生成基因锁定模型的快速方法

    公开(公告)号:US20120017289A1

    公开(公告)日:2012-01-19

    申请号:US12895913

    申请日:2010-10-01

    IPC分类号: C12N15/85

    摘要: The present invention provides a novel method of generating knock down models by electroporation of shRNA construct into the testis. The present invention provides an ethically superior, non-surgical, user friendly rapid method for the generation of permanent lines of shRNA knock down non human vertebrates. This invention is ethically superior as it does not involve any loss of animal life and drastically minimizes the production time and use of animals. Current techniques for making knockout models are cumbersome, require trained personnel, costly infrastructure and require hundreds of eggs collected after killing several females. In contrast, this method neither involves any costly infrastructure nor requires trained personnel. The invention also relates to the quick incorporation of shRNA gene construct into the germline of a species so that shRNA is inheritable. The present invention also generates in a single go a variety of knock down models differentially expressing gene specific shRNA, depending on differential shRNA gene incorporation in native genome of various male germ cells, so that there is no restriction in the choice of the gene knock down.

    摘要翻译: 本发明提供了一种通过将shRNA构建体电穿孔进入睾丸来产生敲除模型的新方法。 本发明提供了一种伦理上优于非手术的,用户友好的快速方法,用于产生shRNA敲除非人脊椎动物的永久性线。 本发明在伦理上是优越的,因为它不涉及动物生命的任何损失,并且极大地最小化了动物的生产时间和使用。 目前用于制作敲除模型的技术很麻烦,需要经过培训的人员,昂贵的基础设施,并且在杀死几名女性后需要收集数百个鸡蛋。 相比之下,这种方法既不涉及昂贵的基础设施,也不需要经过培训的人员。 本发明还涉及将shRNA基因构建体快速并入种的种系,以使shRNA是可遗传的。 本发明还单独地产生差异表达基因特异性shRNA的各种敲低模型,这取决于不同的shRNA基因在各种雄性生殖细胞的天然基因组中的掺入,使得在基因敲除的选择上没有限制 。

    Mechanism-based inhibitors of transthyretin amyloidosis: studies with biphenyl ethers and structural templates
    7.
    发明申请
    Mechanism-based inhibitors of transthyretin amyloidosis: studies with biphenyl ethers and structural templates 审中-公开
    基于机制的转甲状腺素蛋白淀粉样变性抑制剂:联苯醚和结构模板的研究

    公开(公告)号:US20100190832A1

    公开(公告)日:2010-07-29

    申请号:US12587990

    申请日:2009-10-15

    申请人: Avadhesha Surolia

    发明人: Avadhesha Surolia

    摘要: Transthyretin (TTR), a tetrameric thyroxine (T4) carrier protein, is associated with a variety of amyloid diseases. Derivative of biphenyl ethers (BPE), which are shown to interact with a high affinity to its T4 binding site thereby preventing its aggregation and fibrillogenesis. They prevent fibrillogenesis by stabilizing the tetrameric ground state of transthyretin. Two compounds (2-(5-mercapto-[1,3,4]oxadiazol-2-yl)-phenol and 2,3,6-trichloro-N-(4H-[1,2,4]triazol-3-yl) exhibit the ability to arrest TTR amyloidosis. The dissociation constants for the binding of BPEs and compound 11 and 12 to TTR correlate with their efficacies of inhibiting amyloidosis. They also have the ability to inhibit the elongation of intermediate fibrils as well as show nearly complete (>90%) disruption of the preformed fibrils. Biphenyl ethers and compounds 11 and 12 as very potent inhibitors of TTR fibrillization and inducible cytotoxicity.

    摘要翻译: Transthyretin(TTR)是四聚体甲状腺素(T4)载体蛋白,与多种淀粉样蛋白病有关。 联苯醚(BPE)的衍生物,其显示出与其T4结合位点的高亲和力相互作用,从而防止其聚集和原纤维发生。 它们通过稳定转甲状腺素蛋白的四聚体基态来预防原纤维发生。 两种化合物(2-(5-巯基 - [1,3,4]恶二唑-2-基) - 苯酚和2,3,6-三氯-N-(4H- [1,2,4]三唑-3-基) 表现出阻止TTR淀粉样变性的能力,BPE和化合物11和12与TTR的结合的解离常数与其抑制淀粉样变性的功效相关,它们还具有抑制中间原纤维伸长的能力以及近似于 联苯醚和化合物11和12作为TTR纤维化和诱导性细胞毒性的非常有效的抑制剂,完全(> 90%)破裂。

    Novel Bioconjugates As Therapeutic Agent and Synthesis Thereof
    8.
    发明申请
    Novel Bioconjugates As Therapeutic Agent and Synthesis Thereof 有权
    新型生物缀合物作为治疗剂及其合成

    公开(公告)号:US20090088372A1

    公开(公告)日:2009-04-02

    申请号:US12234233

    申请日:2008-09-19

    IPC分类号: A61K38/08 A61P31/12

    摘要: The present disclosure relates to a novel enzymatic approach according to the invention using an unprecedented sortase-catalyzed transpeptidation reaction between a substrate comprising LPXTG peptide motif and biomolecules such as aminosugars, hydroxyamino acids, hydroxyamino acid esters, aminolipids, polyamines; nucleic acids or derivatives thereof, or any molecule having such moieties; or any compound having such moieties to obtain a bioconjugates useful for target delivery of a compound. The present disclosure provides bioconjugates obtained by the novel sortase catalysed transpeptidedation reaction.

    摘要翻译: 本公开涉及根据本发明的新型酶促方法,其使用在包含LPXTG肽基序和生物分子如氨基糖,羟基氨基酸,羟基氨基酸酯,氨基脂肪,多胺的底物之间进行前所未有的分选酶催化的转肽反应; 核酸或其衍生物,或具有这些部分的任何分子; 或具有这种部分的任何化合物,以获得可用于目标递送化合物的生物缀合物。 本公开提供了通过新型分选酶催化的转肽反应获得的生物缀合物。

    Dnazymes for Inhibition of Japanese Encephalitis Virus Replication
    9.
    发明申请
    Dnazymes for Inhibition of Japanese Encephalitis Virus Replication 审中-公开
    抑制日本脑炎病毒复制的Dnazymes

    公开(公告)号:US20090010907A1

    公开(公告)日:2009-01-08

    申请号:US11721596

    申请日:2005-12-14

    摘要: The present invention relates to synthetic catalytic DNA molecules or DNAzymes which specifically cleave the RNA sequences of the Japanese Encephalitis Viral genome and is useful in treating Japanese Encephalitis infection. The DNAzyme comprises of a chemical modification, a catalytic domain and two hybridizing arms. The DNAzymes are 29-45 nucleotides in length. The 3′ end of the DNAzyme is tethered to a poly-(G)10 tail (SEQ ID NO: 46) and the molecule comprises of at least one chemical modification. The chemical modifications are in the form of sugar modification, nucleic acid base modification, and/or phosphate backbone modification. The catalytic DNA molecule inhibits JEV replication in vitro in cultured cells and in vivo in the mouse brain. The present invention also relates to the method of treatment of Japanese encephalitis comprising the steps of introducing the catalytic DNA molecule or DNAzyme into the infected cells under conditions suitable for cleavage and reduction of viral titres.

    摘要翻译: 本发明涉及特异性切割日本脑炎病毒基因组的RNA序列的合成催化DNA分子或DNA酶,可用于治疗日本脑炎感染。 DNAzyme由化学修饰,催化结构域和两个杂交臂组成。 DNA酶长度为29-45个核苷酸。 DNA酶的3'端连接到聚(G)10尾(SEQ ID NO:46),并且分子包含至少一种化学修饰。 化学修饰是糖修饰,核酸碱基修饰和/或磷酸酯骨架修饰的形式。 催化DNA分子在培养细胞中体外抑制JEV复制,并在小鼠脑中体内抑制。 本发明还涉及治疗日本脑炎的方法,包括以下步骤:在适合于切割和还原病毒滴度的条件下将催化DNA分子或DNA酶引入感染的细胞中。

    Anti-cancer utility of HCG vaccines
    10.
    发明授权
    Anti-cancer utility of HCG vaccines 失效
    HCG疫苗的抗癌效用

    公开(公告)号:US5762931A

    公开(公告)日:1998-06-09

    申请号:US295774

    申请日:1994-11-07

    摘要: This invention relates to a method of combatting cancer which cancer releases chorionic gonadotropin or a subunit thereof present in a mammal which method comprises administering to said animal an anti-cancer effective amount of a birth-control vaccine or an antibody to said chorionic gonadotropin or subunit thereof. Birth-control vaccines which are polyvalent vaccines and birth-control vaccines which employ recombinant organisms incorporating sequences coding for reproductive hormones are of particular interest as well as polyclonal and monoclonal antibodies to the chorionic gonadotropin.

    摘要翻译: PCT No.PCT / US92 / 11333 Sec。 371日期:1994年11月7日 102(e)日期1994年11月7日PCT提交1992年12月31日PCT公布。 公开号WO94 / 15633 日期:1994年7月21日本发明涉及一种抗癌药物的方法,所述方法包括向所述动物施用抗癌有效量的避孕疫苗或抗体, 所述绒毛膜促性腺激素或其亚单位。 作为多价疫苗的避孕疫苗和使用含有编码生殖激素的序列的重组生物的避孕疫苗是特别有意义的,以及对绒毛膜促性腺激素的多克隆和单克隆抗体。