FAM46C CRISPR Activation Plasmid (h): sc-407319-ACT

FAM46C (also known as TENT5C) encodes a non-canonical poly(A) polymerase implicated in post-transcriptional control of mRNA stability and protein output, with prominent roles in secretory and differentiation programs. In immune and plasma cell contexts, FAM46C has been linked to regulation of immunoglobulin production and broader endoplasmic reticulum proteostasis, positioning it within pathways governing RNA metabolism, unfolded protein response, and secretory pathway homeostasis. Altered FAM46C activity is frequently studied in hematologic disease biology, particularly multiple myeloma, where changes in its function are associated with dysregulated plasma cell fitness and stress signaling. These features make FAM46C a useful target for dissecting RNA tailing–dependent regulation of gene expression and secretory cell state transitions in human model systems.

FAM46C CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous FAM46C expression without altering the underlying DNA sequence.

FAM46C CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the FAM46C 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 FAM46C transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous FAM46C expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native FAM46C locus and enabling the study of FAM46C-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of FAM46C pathway restoration in tumor cells with silenced or reduced FAM46C expression.

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