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The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas9) system is an adaptive immune response defense mechanism used by archea and bacteria for the degradation of foreign genetic material. This mechanism can be repurposed for other functions, including genomic engineering for mammalian systems, such as gene knockout (KO) and gene activation. CRISPR Activation Plasmid products enable the identification and upregulation of specific genes by utilizing a D10A and N863A deactivated Cas9 (dCas9) nuclease fused to a VP64 activation domain, in conjunction with sgRNA (MS2), a target-specific sgRNA engineered to bind the MS2-P65-HSF1 fusion protein. This synergistic activation mediator (SAM) transcription activation system provides a robust system to maximize the activation of endogenous gene expression.