Gene editing has emerged as a powerful approach for targeting the genetic causes of disease, yet delivering the editing machinery into the correct cells efficiently, safely, and at the scale needed for therapies remains one of the biggest bottlenecks. Among the leading delivery vehicles are engineered virus-like particles (eVLPs), which can enter human cells similar to viruses but carry no viral genes. Instead, these delivery vehicles carry gene editing tools for therapeutic applications. In a new study published in Nature Communications titled, “Genome-wide screening reveals producer-cell modifications that improve virus-like particle production and delivery potency,” researchers from Whitehead Institute have developed a platform that systemically identifies which genes drive or block particle assembly to engineer cells that yield more potent delivery vehicles. “We can engineer the particles as much as we want, but if we don’t understand how the producer cells are actually making the particles, we’re limited in how much we can improve production,” said Aditya Raguram, PhD, Valhalla Fellow at Whitehead Institute and corresponding author of the study. As virus-like particles are assembled inside cultured human cells, the authors ran a genome-wide search to identify which genes are crucial in the production process by generating a large pool of producer cells in which nearly every gene in the human genome was switched off in the population. This approach generates eVLPs loaded with guide RNAs that identify the genetic perturbation in the cell that produced a particular particle. The team could then identify which gene shutdowns enabled and disabled particle production. “One thing that surprised me was how clearly the search was able to highlight specific pathways that play a major role in the production of these particles,” said Diana Ly, research technician at Whitehead Institute and first author of the study. The single gene whose removal most boosted production normally…
