The primary objective of my research is to develop a toolkit of synthetic regulatory factors for targeted epigenome manipulation. Through recruiting numerous synthetic constructs, derived from human chromatin regulators, to genomic regions of interest; the ability of these factors to alter the epigenome will be determined via profiling the downstream transcriptional changes. Traditionally, the Chromium NextGEM single-cell RNA sequencing (scRNA-seq) technology (10x Genomics) has successfully quantitated the expression of synthetic factors and target genes by means of further targeted enrichment of these sequences. However, the requirement of fresh cells limits the number of synthetic constructs that can be tested within a single experiment. The recently published Fixed RNA profiling (“RNA flex”) platform offers a potential solution, enabling multiplexing of many conditions through fixing cells in advance, and its probe-based technology eliminates additional enrichment steps. To compare these two platforms in detecting synthetic constructs, the two experimental procedures were performed in parallel on matched cells: engineered HEK293T cells transduced with a small pool of synthetic constructs. As only a whole transcriptome probe panel is supplied for RNA flex, custom probes were designed such that each synthetic construct and target gene was covered by three non-overlapping probes. Sequencing outputs revealed that metrics including the number of cells captured, the read captured per cell and the total genes detected, were comparable across both platforms. Similar numbers of cells were classified across each synthetic construct and the transcriptional changes across each target gene, modified by different synthetic factors, were equivalent across the two platforms. A subsequent pilot experiment also validated the capability of multiplexing custom RNA flex probes in capturing synthetic constructs. Moving forward, the RNA Flex platform presents a promising technology to enable large-scale detection and assessment of custom synthetic constructs.