X-MAN Models
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GENESIS™ has already been deployed in the engineering of over 350 genetically defined cancer models (with over 200 new cell-lines under commission) that accurately recapitulate the main genetic mutations that lead to lung, breast, colorectal, prostate and many other forms of cancer (see products for full list of available genotypes).
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The most important feature of such cell-lines is that DNA-modifications are always made in endogenous genes. Only in this way can researchers accurately model either the exact disease causing mutations that occur in cancer patients, or the single nucleotide polymorphism’s (SNPs) that predispose patients to a range of genetic-linked diseases, such as cancer, diabetes or heart disease. The second most important feature is that by adding or removing a target mutation; a perfectly matched ‘isogenic’ daughter cell-line is provided; enabling the definitive study of the effects of that gene on a cells phenotype and its subsequent response to a novel drug candidate, or combination’s thereof. The range of cell-types that can be engineered is extensive and includes both normal and cancer cells. Modifying normal cells was rarely attempted before GENESIS but now panels of single and multiple genetic mutations are being introduced into normal cells to begin the process of modeling how cancer manifests itself in real patients. In normal (immortalised) cell-backgrounds (e.g., MCF10a) oncogenic mutations (e.g., PI3K) are ‘knocked-in’ resulting in a gain-of-function, or both alleles of a chosen tumour suppressor gene (e.g., PTEN) are ‘knocked-out’ resulting in a loss of function. In contrast, in pre-existing cancer cell-lines, the mutant allele (e.g., p53 in HCT116) can also be ‘knocked-out’, or corrected. GENESIS is unique in its ability to perform this variety of genetic alterations at any given endogenous locus of human cells. |
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