Next-Generation Targeting Has Organelle-Level Precision

Intracellular organelles are relatively autonomous sub-systems within the cell, whose activity and chemical composition reflect the cell’s metabolic state. Metabolism is altered in diseased or aging cells, reflected at the level of specific organelles within them. Often, introducing compensatory changes in organelles can restore cells to normalcy given the intrinsic feedback between cells and their organelles. Nature already targets the delivery of exogenous cargo with organelle-level precision in living organisms as evidenced by invading pathogens as well as endogenous signaling molecules. DNA can be self-assembled into molecularly precise, well-defined, synthetic assemblies on the nanoscale, commonly referred to as designer DNA nanodevices. Over the last decade, Dr. Krishnan’s lab developed a way to target DNA nanodevices to specific cells in vivo, but with organelle-level precision. The first discovery in 2011 revealed that DNA nanodevices could reach organelles called lysosomes in specific cells of live nematodes, where it functioned as a reporter of pH. Until this innovation, it was not at all obvious whether such DNA nanodevices could function inside a living cell without being interfered with, or interfering with, the cell's own networks of DNA control. The team spent 10 years studying the environment within lysosomes. This presentation will explain how lysosomes can be used to control cell state, flip the cell "from baddie to goodie," and turn cold tumors hot in mice.