VLP delivery and industrial biotech
- Whitehead Institute researchers reported on April 24 that re-engineering the human cells used to make engineered virus-like particles raised gene-editing delivery potency in cultured cells and mice. - The Nature Communications study found producer-cell changes increased cargo packaging and lifted delivery potency by 2- to 9-fold across several cargo types, particle designs, and target cells. - Separately, a Trends in Biotechnology paper described engineering Erwinia strain LJJL01 to turn biomass and plastic feedstocks into muconate and polyhydroxybutyrate, widening biotech uses beyond therapeutics. (nature.com) (sciencedirect.com)
Virus-like particles are shells that act like empty delivery vans: they enter cells like viruses, but they do not carry viral genes. Whitehead Institute researchers said April 24 they made those vans more potent by re-engineering the human cells that manufacture them. (whitehead.mit.edu) (nature.com) The study, published April 24 in Nature Communications, was led by Aditya Raguram and first author Diana Ly. The team ran a genome-wide screen in producer cells to test how shutting off individual human genes changed particle assembly, cargo loading, and final delivery performance. (nature.com) (whitehead.mit.edu) Each engineered virus-like particle carried a genetic tag showing which producer-cell gene had been switched off in the cell that made it. Reading those tags let the team identify genes that helped or blocked production, then build producer cells that packaged more guide RNA cargo. (nature.com) (whitehead.mit.edu) The paper reported a 2- to 9-fold increase in delivery potency across several cargo types, particle systems, and target-cell types in culture and in mice. The gain also carried over to four other delivery-vehicle systems from other labs, according to Whitehead’s summary of the work. (nature.com) (whitehead.mit.edu) That matters because gene editing often stalls at the delivery step, not the editing chemistry itself. Virus-like particles are being pursued as a middle ground between classic viral vectors, which can persist, and nonviral systems, which can struggle to enter cells efficiently. (nature.com) (link.springer.com) A separate paper this month points to a different frontier for engineered biology: using unusual bacteria as industrial workhorses. In a Trends in Biotechnology article available online April 19, researchers described domesticating Erwinia spp. strain LJJL01 as a chassis for biorefinery production. (sciencedirect.com) (cell.com) LJJL01 was isolated from waste charcoal in Colorado and later sequenced as a complete genome. The strain can use sugars, acids, polyols, and aromatic compounds, traits that make it useful for converting mixed waste streams that defeat more standard lab microbes. (journals.asm.org) (sciencedirect.com) The Trends in Biotechnology paper said researchers engineered LJJL01 to make cis,cis-muconate from plastic-derived terephthalate and polyhydroxybutyrate from lignocellulosic hydrolysate. Those are two standard biorefinery targets: muconate is a platform chemical, and polyhydroxybutyrate is a biodegradable polyester. (sciencedirect.com) (cell.com) The through line is that both papers focus on the factory, not just the payload. One retools mammalian cells to ship gene editors more efficiently; the other retools a nonmodel bacterium to turn low-value biomass and plastic into higher-value chemicals. (nature.com) (sciencedirect.com) Both projects are still preclinical or precommercial. But together they show how engineering the production host — the cell that makes the particle or the microbe that runs the fermentation — is becoming a central lever in both therapeutic delivery and industrial biotechnology. (nature.com) (sciencedirect.com)
