Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Abstract

Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8+ T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression

“…Numerous nano constructs have been designed to address each of these elements (32,34,35,68,69); our approach comprehensively combines the favorable benefits of several modalities. It builds on the blood vessel-targeting capacity of the customizable 7C1 lipopolymeric nano vehicle, which has excellent safety profiles (14,15,23,70). The 7C1 delivery system ensures dual strength in direct delivery to the tumor cellular core (where the great majority of BTICs reside) and vasculature-associated invasive niches (11,(44)(45)(46)(47) (where residual resistant populations of BTICs accumulate after a standard therapy regimen).…”

“…The study also exposed the need to improve on the current intracranial distribution of nano therapeutics beyond experimental models of CED using Alzet s.c. osmotic pumps. In addition, nontransient RNA-based nanomedicine therapies using new genome-editing tools, such as the rapidly evolving CRISPR technologies, can be delivered via the customizable LPNPs for sustained elimination of tumorigenic molecular markers (14,70). Furthermore, continued refinement and more customized functionalization of the NPs via surface chemistry engineering may allow antitumor gene editing in multiple cell types present in the tumor microenvironment (e.g., in immune cells and astrocytes) which can be recruited in a locally coordinated antimalignancy campaign to boost therapeutic durability and efficiency.…”

Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals

“…Tools for effective transfer of exogenous mRNA into cells in the body would advance a rapidly emerging class of gene therapy drugs with the potential to transform the treatment of illnesses as diverse as cancer, genetic disorders, and infectious diseases (1,2). Delivery and subsequent expression of mRNA into its encoded protein can be leveraged for a wide range of research, imaging, and therapeutic applications including protein replacement or augmentation therapy and new vaccine strategies either for prophylactic or immunotherapeutic approaches (3)(4)(5)(6)(7). Although gene transfer studies of other oligonucleotides such as plasmid DNA and siRNA have dominated the gene delivery field for some time (8)(9)(10)(11)(12)(13), the use of mRNA to generate therapeutic proteins has received attention only recently (1,(14)(15)(16).…”

Bubbled RNA‐Based Cargo for Boosting RNA Interference

“…Ribonucleic acid (RNA) has attracted considerable attention for its potential applications in nanomedicine for the treatment of cancer or infectious disease as well as for immunization 1. In addition to its range of inherent biological activities, molecular simplicity, and ease of modification have also accelerated the progress of RNA nanotechnology 2.…”