Tyk 2 CRISPR Activation Plasmid (h): sc-400902-ACT

Human TYK2 encodes the non-receptor tyrosine kinase Tyk2, a Janus kinase family member that couples type I and type III interferon receptors and multiple interleukin receptors to downstream STAT phosphorylation and transcriptional programs. Tyk2-dependent signaling modulates innate and adaptive immune responses, shaping cytokine production, antigen presentation, and inflammatory gene expression through the JAK–STAT pathway. Genetic and functional perturbations in TYK2 are linked to immune dysregulation, with relevance to infection susceptibility, chronic inflammatory phenotypes, and autoimmunity-associated signaling states. As a pathway node, TYK2 is widely studied for its role in cytokine receptor crosstalk and context-dependent control of interferon-stimulated gene networks.

Tyk 2 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous TYK2 expression without altering the underlying DNA sequence.

Tyk 2 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the TYK2 locus in human cell lines. The system is built around a catalytically inactive Cas9 (dCas9) carrying two inactivating mutations (D10A and N863A) that eliminate nuclease activity while preserving DNA binding. This dCas9 is fused to VP64, a potent transcriptional activator, and is co-expressed with a blasticidin resistance gene for selection. The second plasmid encodes the MS2-p65-HSF1 fusion protein, a secondary activator complex that works in concert with dCas9-VP64, alongside a hygromycin resistance gene. The third plasmid encodes a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers that recruit the MS2-p65-HSF1 complex to the activation site, accompanied by a puromycin resistance gene. The three plasmids are delivered at a 1:1:1 mass ratio for balanced expression of all system components.

Once assembled at the target locus, the SAM complex binds within approximately 200 bp upstream of the TYK2 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous Tyk 2 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native TYK2 locus and enabling the study of Tyk 2-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of Tyk 2 pathway restoration in tumor cells with silenced or reduced TYK2 expression.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.