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Synthesis

Dendrimer-RNA nanoparticles offer fast, customizable vaccines

Researchers design particles carrying self-replicating RNAs to produce immunity against H1N1, Ebola, and malaria-like parasite in mice

by Michael Torrice
July 11, 2016 | APPEARED IN VOLUME 94, ISSUE 28

Vaccine production can be time-consuming. For example, it takes about six months to produce sufficient amounts of the seasonal influenza vaccine.

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Credit: Proc. Natl. Acad. Sci. USA
These vaccine nanoparticles, which are about 150 nm wide, consist of a self-assembled core of amine-based dendrimer (yellow) and replicon RNA (red). A lipid-modified polyethylene glycol (blue) coating surrounds the particles.
Credit: Proc. Natl. Acad. Sci. USA
These vaccine nanoparticles, which are about 150 nm wide, consist of a self-assembled core of amine-based dendrimer (yellow) and replicon RNA (red). A lipid-modified polyethylene glycol (blue) coating surrounds the particles.

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, amine-based 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.

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