The Elegance of Viruses 2

The Elegance of Viruses 2

Mohamad Najia, Anna Le, Paul Blainey

Koch Institute at MIT, Broad Institute, MIT Department of Biological Engineering

Viruses are molecular machines that have evolved to package and export their genetic material from cells. We were inspired by viruses and repurposed viral machinery to impart new, synthetic functions to human cells. Current technologies that are employed to understand cellular biology exhibit a fundamental problem: cells are destroyed in the act of making transcriptional measurements. However, we overcame this challenge by repurposing viral machinery to manufacture representative samples of a cell’s RNA within viruses, which are then secreted from the cell. We can then purify these virus particles and measure the RNA inside to get a live-cell readout of a cell’s transcriptional state. We believe this technology is a substantial technological advance that will enable scientists to answer new types of questions that have previously been infeasible with destructive measurement approaches.

We utilized and repurposed viral machinery from the murine leukemia virus (MLV) as the basis of our technology. Our approach was to express the core MLV structural protein, Gag, which is sufficient to create virus-like particles. We then fused Gag to a fluorescent protein and expressed this fusion protein with human cells to track the assembly of virus-like particles.

We think this image crystalizes the elegance of viruses and their broad utility to be used as molecular substrates to impart novel synthetic functions into mammalian cells.

Bright green and blue cluster like structures in a black background

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