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Why is gene editing better than transgenesis

Transgenesis is the process of introducing an exogenous gene into a living organisms, where it is either transiently expressed (for example from a plasmid), or stably expressed through random integration into the genome. In mammalian cells, lines that stably express a transgene of interest at desirable levels can be isolated by drug selection and screening. In this way scientists can perform gain of function analyses and study the role that genes of mutations play in specific biological pathways, or in disease. Effects on Gene ExpressionHowever, the generation of these lines through random integration can lead to several confounding effects on gene expression, including multiple integrations per cell, the activation or disruption of endogenous genes at or near the site of integration, and unstable expression of the transgene due to epigenetic modifications. These, coupled with the constitutive and often high expression levels of the transgene can lead to unpredictable cell behavior and irreproducible or hard to interpret results. Targeted gene editing overcomes these limitations by introducing modifications at the endogenous locus of the gene (and only this site), such that they are expressed from the native promoter. Consequently, the effect of gain of function can be studied in a physiological context. The advantages of using gene editing vs transgenesis are highlighted when one compares the overexpression of an oncogene vs the gene edited equivalent. Overexpression of oncogenic PIK3CA results in transformation of normal mammary epithelial cells, while knockin of the same variants does not