As we further understand the complexity and diversity of cellular states, it is becoming necessary for a cellular engineering toolbox, consisting of molecular tools that allow control over cell states and types. Drawing from a combination of natural discovery and rational engineering, we will discuss our lab's recent work in this area. We will discuss RNA, DNA, and cell targeting approaches, including the novel CRISPR effector, Cas7-11, that can be used to target transcripts in mammalian cells for degradation, with reduced toxicity; a new genome insertion system, PASTE, that enables efficient, programmable insertion of large DNA segments into the genome without limitations of previous genome editing approaches; and a new approach for control of cell states, RADARS, that can sense and react to transcript levels in cells. These technologies form the basis for new approaches to manipulate and understand cellular states, with implications in basic biology, diagnostics, and therapeutics.
1. Identify applications of novel RNA-targeting CRISPR systems.
2. Distinguish between CRISPR effectors, including Cas13 and Cas7-11, their effects on mammalian cells, and their potential therapeutic uses.
3. Identify applications of genome insertion approaches and relative advantages of different genome insertion technologies, including PASTE.