公开(公告)号：US20030180953A1

公开(公告)日：2003-09-25

申请号：US10032585

申请日：2001-12-20

申请人： Elitra Pharmaceuticals, Inc.

发明人： Terry Roemer ,  Bo Jiang ,  Charles Boone ,  Howard Bussey ,  Kari L. Ohlsen

IPC分类号： C12N001/18 ,  C12N001/16 ,  C12N015/74

CPC分类号： C12N15/1082 ,  C07K14/37 ,  C07K14/40 ,  C12R1/645 ,  C12R1/725

摘要： The present invention provides methods and compositions that enable the experimental determination as to whether any gene in the genome of a diploid pathogenic organism is essential, and whether it is required for virulence or pathogenicity. The methods involve the construction of genetic mutants in which one allele of a specific gene is inactivated while the other allele of the gene is placed under conditional expression. The identification of essential genes and those genes critical to the development of virulent infections, provides a basis for the development of screens for new drugs against such pathogenic organisms. The present invention further provides Candida albicans genes that are demonstrated to be essential and are potential targets for drug screening. The nucleotide sequence of the target genes can be used for various drug discovery purposes, such as expression of the recombinant protein, hybridization assay and construction of nucleic acid arrays. The uses of proteins encoded by the essential genes, and genetically engineered cells comprising modified alleles of essential genes in various screening methods are also encompassed by the invention.

摘要翻译： 本发明提供了能够对二倍体致病生物体的基因组中的任何基因是否必需的实验测定以及是否需要毒力或致病性的方法和组合物。 该方法包括构建遗传突变体，其中特定基因的一个等位基因被灭活而基因的其他等位基因置于条件表达下。 识别必需基因和对致病性感染发展至关重要的那些基因，为开发针对这种致病生物的新药筛选提供了基础。 本发明进一步提供了被证实是必需的白念珠菌基因，并且是药物筛选的潜在靶标。 靶基因的核苷酸序列可以用于各种药物发现目的，例如重组蛋白的表达，杂交测定和核酸阵列的构建。 在各种筛选方法中，由必需基因编码的蛋白质的使用以及包含必需基因的修饰的等位基因的遗传工程改造的细胞也包括在本发明中。