Applications of single-cell RNA sequencing in drug discovery and development.

Single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq) methods, together with associated computational tools and the growing availability of public data resources, are transforming drug discovery and development. New opportunities are emerging in target identification owing to improved disease understanding through cell subtyping, and highly multiplexed functional genomics screens incorporating scRNA-seq are enhancing target credentialling and prioritization. ScRNA-seq is also aiding the selection of relevant preclinical disease models and providing new insights into drug mechanisms of action. In clinical development, scRNA-seq can inform decision-making via improved biomarker identification for patient stratification and more precise monitoring of drug response and disease progression. Here, we illustrate how scRNA-seq methods are being applied in key steps in drug discovery and development, and discuss ongoing challenges for their implementation in the pharmaceutical industry.

Specific knockdown of the D2 long dopamine receptor variant.

Dopamine signaling in the nucleus accumbens is critical in mediating the effects of cocaine. There are two splice variants of dopamine D2 receptors, D2L and D2S, which are believed to have different functional roles. Here, we show, that knocking down D2L selectively using viral-mediated short-hairpin RNA led to a slight but significant decrease in basal locomotor activity with no significant change in cocaine-induced stimulation of locomotion. The knockdown appears to produce a trend of reduced conditioned place preference to cocaine but the difference was not statistically significant. Our results demonstrated that the splice variants of D2 receptors can be selectively manipulated in vivo in specific brain regions allowing more specific studies of each D2 receptor isoform.