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Phenotypic conversion of cells mediated by external guide sequences

机译:外部指导序列介导的细胞表型转化

摘要

Disclosed are a method and compositions for delivering nucleic acids to bacterial cells. The method does not require manipulation of the bacteria and is therefore particularly suited to delivery of nucleic acids to bacteria in natural environments, including inside animals bodies. The method generally involves conjugating the nucleic acid to be delivered with a cationic porphyrin and bringing the conjugate and the target bacterial cells into contact. Both the porphyrin and conjugated nucleic acid are taken up by the bacterial cells and the nucleic acid can then have a biological effect on the cells. Specifically disclosed is a method for converting drug-resistant bacterial cells to drug-sensitive cells by delivery of external guide sequences to the cells which then promote cleavage of RNA molecules involved in conferring the drug-resistant phenotype on the cells. The drug-resistant phenotype of the cells is thus converted to a drug-sensitive phenotype. The drug-sensitive cells are then susceptible to drug therapy. Also disclosed is a method and compositions for killing eukaryotic pathogens or converting drug-resistant eukaryotic cells to drug-sensitive cells. The method involves the delivery of external guide sequences, ribozymes, or vectors encoding external guide sequences or ribozymes, to eukaryotic cells. Preferred target eukaryotic cells for the disclosed method include algae, protozoa, fungi, slime mold, and cells of helminths.
机译:公开了用于将核酸递送至细菌细胞的方法和组合物。该方法不需要操作细菌,因此特别适合于在自然环境中,包括在动物体内,将核酸递送给细菌。该方法通常包括将待递送的核酸与阳离子卟啉偶联,并使偶联物与靶细菌细胞接触。卟啉和缀合的核酸都被细菌细胞吸收,然后核酸可以对细胞产生生物学作用。具体公开了一种通过将外部指导序列递送至细胞而将耐药细菌细胞转化为药物敏感细胞的方法,所述外部引导序列随后促进了参与赋予细胞耐药性表型的RNA分子的裂解。细胞的药物抗性表型因此转化为药物敏感性表型。然后,药物敏感性细胞易受药物治疗。还公开了用于杀死真核病原体或将抗药性真核细胞转化为药敏细胞的方法和组合物。该方法涉及将外部指导序列,核酶或编码外部指导序列或核酶的载体递送至真核细胞。用于所公开的方法的优选靶标真核细胞包括藻类,原生动物,真菌,粘液霉菌和蠕虫细胞。

著录项

  • 公开/公告号US6610478B1

    专利类型

  • 公开/公告日2003-08-26

    原文格式PDF

  • 申请/专利权人 YALE UNIVERSITY;

    申请/专利号US19970912378

  • 申请日1997-08-15

  • 分类号C12Q16/80;C12P210/60;C12N157/40;C07B470/00;

  • 国家 US

  • 入库时间 2022-08-22 00:06:06

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