Synthetic biology devices and circuits for RNA-based ‘smart vaccines’: a propositional review

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.

Implementing Nonlinear Feedback Controllers Using DNA Strand Displacement Reactions

“…Nominal Values S qsm total substrate 4 nM X 3 tuning parameter 0.1 nM k b 1 forward binding rate 10 7 /M/s k b 2 forward binding rate 10 7 /M/s k c 1 catalytic reaction rate 100 q i C max /s k c 2 catalytic reaction rate 50 q i C max /s This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication.…”

“…S EVERAL of the proposed industrial and biomedical applications of synthetic biology require the ability to precisely and robustly control the behaviour of synthetic circuits or devices at a biomolecular level [1], [2]. A fundamental aim of synthetic biology is thus to achieve the capability to design and implement robust embedded biomolecular feedback control circuits [3].…”

Biomolecular implementation of a quasi sliding mode feedback controller based on DNA strand displacement reactions

“…Nominal Values S qsm total substrate 4 nM X 3 tuning parameter 0.1 nM k b 1 forward binding rate 10 7 /M/s k b 2 forward binding rate 10 7 /M/s k c 1 catalytic reaction rate 100 q i C max /s k c 2 catalytic reaction rate 50 q i C max /s Table III and the initial concentrations of the non-auxiliary species in equations (23)-(28) are set to zero, i.e. X 2 0 = A 0 = 0 nM.…”

Synthetic switch-based baculovirus for transgene expression control and selective killing of hepatocellular carcinoma cells

“…aptamer) and an actuator domain have been extensively developed to turn ON/OFF gene expression and can be wired to higher-order synthetic circuits (20–22). However, many of these riboswitches require adding an inducing ligand (20,22,23), thus making its in vivo applications in animals and humans more complicated. RNA switches can also be fabricated by appending miRNA complementary sequences at the 3′ untranslated region (UTR) of transgene to recognize intracellular miRNA and inhibit transgene expression (24).…”

“…In addition, archaeal ribosomal protein L7Ae is an RNA-binding protein that binds with high affinity to RNA motif known as kink-turn (K-turn) and represses subsequent RNA translation (for review see (22)). The interaction of L7Ae:K-turn was first harnessed to construct an OFF switch to repress mRNA translation by inserting K-turn motifs at the 5′ UTR of a reporter gene (27).…”