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Next-generation sequencing (NGS) has increased our understanding of biology by enabling highly sensitive RNA expression analysis across a wide dynamic range. As NGS applications continue to grow, so does the need for more powerful tools to work with less-than-ideal samples. As the core of the SMARTer kits for transcriptome analysis, Clontech’s patented SMART® technology utilizes the template switching activity of reverse transcriptase to enable researchers to analyze their most challenging samples, such as single cells, low-input RNA, noncoding RNA, and RNA from degraded samples. In particular, single-cell RNA-seq is one of the more difficult, and fastest growing, applications of NGS. The high sensitivity and dT-primed protocol of the SMARTer Ultra Low family has made these kits the industry standard for single-cell analysis. Applications of SMART technology are constantly expanding and now include a novel, ligation-free method for generating ChIP (chromatin immunoprecipitation) sequencing libraries. The purpose of this seminar is to take a deeper look into the new technologies being developed for single-cell RNA-seq and other sensitive NGS applications.