UCH-L1 Lentiviral Activation Particles (h2): sc-401088-LAC-2

Human UCHL1 encodes the deubiquitinating enzyme UCH-L1, a neuron-enriched ubiquitin C-terminal hydrolase that maintains ubiquitin homeostasis by processing ubiquitin precursors and ubiquitinated substrates within the ubiquitin–proteasome system. UCH-L1 activity contributes to protein quality control, synaptic function, and axonal integrity, linking it to pathways governing proteostasis, stress responses, and neuronal survival. Dysregulation or mutation of UCHL1 has been associated with neurodegenerative and neurodevelopmental phenotypes, including Parkinson’s disease- and Alzheimer’s disease-related pathology as well as peripheral neuropathies. Gene editing of UCHL1 supports mechanistic studies of ubiquitin signaling, modeling of disease-relevant variants in human cell systems, and evaluation of how altered deubiquitination impacts aggregation, mitochondrial stress, and neuronal differentiation.

UCH-L1 Lentiviral Activation Particles (h2) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient UCHL1 upregulation across a broader range of human cell types.

UCH-L1 Lentiviral Activation Particles (h2) deliver all functional components of the synergistic activation mediator (SAM) system via lentiviral transduction. The system comprises three particle preparations co-transduced into target cells: one encoding catalytically inactive dCas9 (D10A and N863A mutations) fused to the VP64 transactivation domain with a blasticidin resistance gene; one encoding the MS2-p65-HSF1 fusion protein with a hygromycin resistance gene; and one encoding a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers with a puromycin resistance gene. Following lentiviral transduction and genomic integration of the expression cassettes, the SAM components are stably expressed and assemble at the target locus within the proximal promoter region upstream of the UCHL1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous UCH-L1 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native UCHL1 genomic locus and regulatory architecture.

The lentiviral format offers several practical advantages: stable genomic integration supports heritable activation across cell divisions; high-titer particle preparations eliminate the need for in-house viral production; and compatibility with primary, non-dividing, and transfection-resistant cell types expands experimental accessibility. Successful transduction can be confirmed and enriched through triple antibiotic selection using puromycin, hygromycin, and blasticidin.

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