Dendrimer-RNA particles offer fast, customizable vaccines - C&EN

During the amplification process, nucleic acid structures that resemble those produced during a viral infection form. This triggers an. View: PDF | Fu...
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Engineered microbes make silver nanoparticles Repurposed bacterial metal-storing compartments could provide greener route to the particles Iron can be scarce in many environments. Thermotoga maritima bacteria and replaced So bacteria stash this essential nutrient it with the sequence for a small protein that within intracellular compartments they can precipitates elemental silver instead. draw from when external sources dry up. Then they transferred the entire genetic Now, scientists have engineered bacteria piece into an easy-to-grow laboratory strain so that their iron-storing compartments of Escherichia coli. As a result, encapsulins in accumulate silver inthe engineered E. coli stead of iron, allowing stuffed themselves researchers to prowith silver from their duce silver nanoparsurroundings, forming ticles for industrial symmetrical nanoparuses (ACS Synth. Biol. ticles about 13 to 15 nm 2016, DOI: 10.1021/ in diameter. acssynbio.6b00117). When tested Silver nanopartiagainst five laboratory cles—commonly used strains of bacteria, as antimicrobials in including common bandages, clothing, pathogens such as Saland other products— monella typhimurium, are usually manufacthe isolated nanopartured at industrial Elemental silver accumulates inside ticles had twice as scales in processes encapsulins to make 13- to 15-nmmuch antimicrobial that use high temdiameter silver particles, shown in this activity as commerperatures or large transmission electron micrograph. cially available silver amounts of chemical nanoparticles or silver reagents. With the new engineered bactesalts. This surprisingly strong activity could ria, the researchers say, silver nanoparticles be because the microbe-made particles are could potentially be mass-produced by fermore uniformly sized than typical commermenting microbes in ways similar to those cial mixes, says David F. Savage of the Uniused to make vitamins, antibiotics, or beer. versity of California, Berkeley. To make these minuscule metal globs, In the past, researchers have made mePamela A. Silver and Tobias W. Giessen of tallic nanostructures using virus particles or Harvard University turned to a 20-sided another iron-storing protein known as ferricapsulelike structure in bacteria known as tin. But it wasn’t previously possible to make encapsulin, which holds iron-storing prosilver nanoparticles in the size range formed teins that pack the capsule full of the metal. by encapsulins, Giessen says, which is esThe researchers removed the gene that ensential for antimicrobial activity.—JYOTI codes encapsulin’s iron-storing protein in MADHUSOODANAN, special to C&EN

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DendrimerRNA particles offer fast, customizable vaccines Vaccine production can be time-consuming. For example, it takes about six months to produce sufficient amounts of the seasonal influenza vaccine. A team of researchers led by Jasdave S. Chahal of the Whitehead Institute for Biomedical Research and Omar F. Khan of Massachusetts Institute of Technology now reports a nanoparticle-based vaccine platform that can be made in about a week and could target multiple pathogens at once (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1600299113). The payload for the team’s nanoparticles is a special type of messenger RNA that encodes two proteins: one that can copy the mRNA and another that is an antigen of the targeted pathogen. When this “replicon” mRNA gets inside cells, the first protein amplifies the mRNA, leading to the production of large amounts of the antigen. During the amplification process, nucleic acid structures that resemble those produced during a viral infection form. This triggers an immune response, leading to the production of antibodies against the produced antigens. To deliver the replicon mRNA, Khan designed an ionizable, aminebased dendrimer that can self-assemble with nucleic acids to form nanoparticles. Particles form no matter which antigen the replicon codes for. Also, the particles can hold large amounts of mRNA, so each particle could stimulate a response to multiple antigens at once. The team demonstrated that the particles could protect mice from infections by H1N1 influenza, Ebola virus, and Toxoplasma gondii, a malaria-like parasite. The T. gondii particles targeted six different antigens from the parasite.—MICHAEL TORRICE

CREDIT: ACS SYNTH. BIOL.

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