Self-amplifying RNA vaccines

Vaccination Vaccines are a triumph of medicine and science – but is the pipeline running dry? What about all those viruses we have not been able to make effective vaccines against – HIV, RSV, Ebola, etc? DNA vaccines have generally proved to be disappointing in clinical trials. This interesting new paper in PNAS suggests possible future strategies.


Nonviral delivery of self-amplifying RNA vaccines. PNAS USA 20 August2012, doi: 10.1073/pnas.12093671
Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.

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3 Responses to Self-amplifying RNA vaccines

  1. Ed Rybicki says:

    …so: liposomes to deliver what amounts to a viral RNA that can’t make particles? OK…this is new, how??

  2. Ed Rybicki says:

    …and having seen the paper, I note:
    “The RNA was produced in vitro by an enzymatic transcription reaction from a linear pDNA template using a T7 RNA polymerase, thereby avoiding safety concerns and complex manufacturing issues associated with cell culture production of live viral vaccines, recombinant subunit proteins, and viral vectors.”
    Yes: and making the delivery SOOOOOOO incredibly expensive as to be totally impractical for any purposes other than a proof of concept – and it really isn’t anything newer than the old Alphavax VEE vector, dressed up with in vitro-synthesised RNA and liposomes.
    So thanks for the paper, Alan, but as far as a vaccine goes – FAIL!!!

  3. AJ Cann says:

    Surely the fact that it’s not just a transcription system to make particles is new?

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