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Trafficking

Understanding trafficking pathways for natural and therapeutics small RNAs

While a wide range of formulations efficiently deliver oligonucleotides to tissues and cells, it is not well realized that only a very tiny fraction of intracellular compounds become biologically functional. Most delivery technologies result in millions of siRNAs internalized per cell while only hundreds of loaded RISC complexes are required to silence the gene. We utilize a combination of TIRF and SIM microscopy (TESM) and quantitative mass spectrometry to visualize and map trafficking pathways involved in internalization and re-localization of native and therapeutic RNAs. We believe that a detailed understanding of this process eventually will allow us to rationally engineer vehicles of siRNA transport that will mimic native trafficking pathways and deliver oligonucleotides directly to the place of biological activity. This project is a collaboration with the labs of Silvia Corvera, Kevin Fogarty, and Victor Ambros.

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