Meet The X-MAN
Horizon and its partners have now deployed GENESIS in the engineering of over 150 genetically defined X-MAN (Mutant And Normal) cancer models 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).
Click on the image to enlarge.
The most important feature of X-MAN 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 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 combinations 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 (Discovery 1 panel) and multiple genetic mutations (Discovery 2 panel) are being introduced into normal cells to begin the process of modeling how cancer manifests itself in patients.
In normal (immortalised) cell-backgrounds (e.g., MCF10a) oncogenic mutations (e.g., PI3K) are ‘knocked-in’, or both alleles of a chosen tumour suppressor gene (e.g., PTEN) are ‘knocked-out’. In contrast, in pre-existing cancer cell-lines, the mutant allele (e.g., p53 in HCT116) is ‘knocked-out’, or corrected.
These gain- or loss-of-function mutant genotypes are embodied in the X-MAN Discovery 1 and Discovery 2 cell panels
Horizon has also built up a large bank of bi-allelic gene knock-outs of non-mutated ‘cancer associated’ genes that are not directly initiating or progressing cancer, but are important mediators of the cancer phenotype. These are embodied in the X-MAN Researcher panel.
References
- GENESIS & X-MAN FAQ (Download)
