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Abstract
Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable ‘smart vaccines’ will revolutionize the field of RNA vaccination.
Acknowledgements
The authors would like to thank K Kariko for critical reading of the manuscript. O Andries was supported by a PhD fellowship and international mobility grant from Fonds Wetenschappelijk Onderzoek (FWO) and the Emmanuel van der Schueren fellowship from Vlaamse Liga tegen Kanker (VLK). K Bodner was supported by the MIT Amgen-UROP Scholars Program. This work was supported by Bijzonder Onderzoeksfonds (BOF) from Ghent University and grants from FWO (G.0235.11N and G.0621.10N) to NN Sanders and grants from the Defense Advanced Research Projects Agency (DARPA) and an innovation award from the Ragon Institute of MGH, MIT and Harvard to R Weiss.
Financial & competing interests disclosure
This work was supported by the research foundation- Flanders (FWO), Belgium; Ghent University, Belgium; Massachusetts Institute of Technology, MA, USA and DARPA, Ragon Institute. T Kitada, K Bodner and R Weiss are named as inventors on a US provisional patent application (62/047137 ‘RNA-based Logic Circuits with RNA Binding Proteins, Aptamers and Small Molecules’) related to the subject of this review. Ownership of the patent, will be transferred to the Massachusetts Institute of Technology if granted by the USPTO. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Synthetic biology aims to engineer living organisms with unprecedented precision, predictability and sophistication.
Synthetic biologists have been compiling a catalog of highly modular and predictable genetic parts and devices.
RNA-binding proteins, synthetic riboswitches, RNAi modulators and protein destabilization tags are among the parts and devices that can be used for post-transcriptional gene regulation.
Composable genetic devices can be assembled into synthetic gene circuits with complex behavior.
Modified and replicating RNA are emerging platforms for gene delivery.
Mammalian synthetic biologists must encode therapeutic gene circuits on RNA for increased safety.
RNA vaccines have been gaining attention as an alternative to standard attenuated pathogen or protein-based vaccines.
RNA-based gene circuits may enable antigen or adjuvant expression to be controlled in a sophisticated manner.
One shot prime-boost circuits or multivalent sequential antigen/adjuvant expression circuits are just a few of the many possible synthetic gene circuit applications for vaccination.
RNA-based ‘smart vaccines’ will revolutionize the field of vaccination by providing solutions to unmet societal needs.