Tipping the Proteome with Gene-Based Vaccines: Weighing in on the Role of Nanomaterials

Table 1

Summary of current data and future direction for gene-based vaccines.

	DNA Vaccines [1–42, 66]	RNA Vaccines [5, 42–55]	Future Direction: RNA and Nanomaterials [6, 53, 55–65, 67–77]
Design	Relatively easy, inexpensive, and quick to construct. Easy to manipulate. Does not require cold chain.	Relatively easy, inexpensive, and quick to construct. Can be produced in large amounts in vitro from DNA template.	Functionalized nanomaterials can be conjugated to further stabilize RNA and to increase penetration.
Delivery	IM injection is most common, but often requires prime/boost. Biolistic bombardment with DNA-coated gold microparticles is currently most efficient. Needle-free delivery via Bioinjector.	Currently, there is no standard delivery method; IM injection is most common. Liposome carriers can also be used.	Gene gun delivery of RNA conjugated with dendrimers and various nanoparticles as stabilizing delivery vehicles.
Stability	Generally stable at room temperature. Long shelf life.	Unstable for storage unless oxidation, hydrolysis, and contact with nucleases are prevented. Quickly degraded in physiological fluid, although studies show unprotected RNA can induce immune response.	Complexing the RNA with multiple nanomaterials can have a compounding effect to increase stability for storage and delivery.
Safety	Considered relatively safe, though there is theoretical risk of insertional mutagenesis after integration, induction of autoimmunity, and transfer of antibiotic resistance.	Rapidly cleared from tissue and does not need to enter nucleus; therefore, there is no risk of insertional mutagenesis after integration, induction of autoimmunity, or transfer of antibiotic resistance.	Continue researching the effect of shape, size, and surface chemistry on biocompatibility and cellular interactions of various nanomaterials.
Immunogenicity	Activate both cellular and humoral pathways. Poor result in human clinical trials. Must be transported to the nucleus in order to exert biological effect.	Activate both cellular and humoral pathways. No need to cross nuclear membrane to exert its biological effect. No need to be replicated or transcribed.	Complex RNA to nanomaterials that recognize and target specific cells. Continue research on nanomaterials that penetrate the cell membrane with adverse cellular effects.