Nanomaterial Delivery Systems for mRNA Vaccines.
Ontology highlight
ABSTRACT:
SUBMITTER: Buschmann MD
PROVIDER: S-EPMC7836001 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Nanomaterial Delivery Systems for mRNA Vaccines.
Buschmann Michael D MD Carrasco Manuel J MJ Alishetty Suman S Paige Mikell M Alameh Mohamad Gabriel MG Weissman Drew D
Vaccines 20210119 1
The recent success of mRNA vaccines in SARS-CoV-2 clinical trials is in part due to the development of lipid nanoparticle delivery systems that not only efficiently express the mRNA-encoded immunogen after intramuscular injection, but also play roles as adjuvants and in vaccine reactogenicity. We present an overview of mRNA delivery systems and then focus on the lipid nanoparticles used in the current SARS-CoV-2 vaccine clinical trials. The review concludes with an analysis of the determinants o ...[more]
Similar Datasets
Project description:In recent years, the use of messenger RNA (mRNA) in the fields of gene therapy, immunotherapy, and stem cell biomedicine has received extensive attention. With the development of scientific technology, mRNA applications for tumor treatment have matured. Since the SARS-CoV-2 infection outbreak in 2019, the development of engineered mRNA and mRNA vaccines has accelerated rapidly. mRNA is easy to produce, scalable, modifiable, and not integrated into the host genome, showing tremendous potential for cancer gene therapy and immunotherapy when used in combination with traditional strategies. The core mechanism of mRNA therapy is vehicle-based delivery of in vitro transcribed mRNA (IVT mRNA), which is large, negatively charged, and easily degradable, into the cytoplasm and subsequent expression of the corresponding proteins. However, effectively delivering mRNA into cells and successfully activating the immune response are the keys to the clinical transformation of mRNA therapy. In this review, we focus on nonviral nanodelivery systems of mRNA vaccines used for cancer gene therapy and immunotherapy.
| S-EPMC8949480 | biostudies-literature
Project description:Messenger ribonucleic acid (mRNA) was found as the intermediary that transfers genetic information from DNA to ribosomes for protein synthesis in 1961. The emergency use authorization of the two covid-19 mRNA vaccines, BNT162b2 and mRNA-1273, is a significant achievement in the history of vaccine development. Because they are generated in a cell-free environment using the in vitro transcription (IVT) process, mRNA vaccines are risk-free. Moreover, chemical modifications to the mRNA molecule, such as cap structures and changed nucleosides, have proved critical in overcoming immunogenicity concerns, achieving sustained stability, and achieving effective, accurate protein production in vivo. Several vaccine delivery strategies (including protamine, lipid nanoparticles (LNPs), polymers, nanoemulsions, and cell-based administration) were also optimized to load and transport RNA into the cytosol. LNPs, which are composed of a cationic or a pH-dependent ionizable lipid layer, a polyethylene glycol (PEG) component, phospholipids, and cholesterol, are the most advanced systems for delivering mRNA vaccines. Moreover, modifications of the four components that make up the LNPs showed to increase vaccine effectiveness and reduce side effects. Furthermore, the introduction of biodegradable lipids improved LNP biocompatibility. Furthermore, mRNA-based therapies are expected to be effective treatments for a variety of refractory conditions, including infectious diseases, metabolic genetic diseases, cancer, cardiovascular and cerebrovascular diseases. Therefore, the present review aims to provide the scientific community with up-to-date information on mRNA vaccines and their delivery systems.
| S-EPMC10405914 | biostudies-literature
Project description:Vaccination was first pioneered in the 18th century by Edward Jenner and eventually led to the development of the smallpox vaccine and subsequently the eradication of smallpox. The impact of vaccination to prevent infectious diseases has been outstanding with many infections being prevented and a significant decrease in mortality worldwide. Cancer vaccines aim to clear active disease instead of aiming to prevent disease, the only exception being the recently approved vaccine that prevents cancers caused by the Human Papillomavirus. The development of therapeutic cancer vaccines has been disappointing with many early cancer vaccines that showed promise in preclinical models often failing to translate into efficacy in the clinic. In this review we provide an overview of the current vaccine platforms, adjuvants and delivery systems that are currently being investigated or have been approved. With the advent of immune checkpoint inhibitors, we also review the potential of these to be used with cancer vaccines to improve efficacy and help to overcome the immune suppressive tumor microenvironment.
| S-EPMC8042385 | biostudies-literature
Project description:Vaccination is still the most cost-effective way to combat infectious illnesses. Conventional vaccinations may have low immunogenicity and, in most situations, only provide partial protection. A new class of nanoparticle-based vaccinations has shown considerable promise in addressing the majority of the shortcomings of traditional and subunit vaccines. This is due to recent breakthroughs in chemical and biological engineering, which allow for the exact regulation of nanoparticle size, shape, functionality, and surface characteristics, resulting in improved antigen presentation and robust immunogenicity. A blend of physicochemical, immunological, and toxicological experiments can be used to accurately characterize nanovaccines. This narrative review will provide an overview of the current scenario of the nanovaccine.
| S-EPMC9694785 | biostudies-literature
Project description:mRNA vaccines have become a versatile technology for the prevention of infectious diseases and the treatment of cancers. In the vaccination process, mRNA formulation and delivery strategies facilitate effective expression and presentation of antigens, and immune stimulation. mRNA vaccines have been delivered in various formats: encapsulation by delivery carriers, such as lipid nanoparticles, polymers, peptides, free mRNA in solution, and ex vivo through dendritic cells. Appropriate delivery materials and formulation methods often boost the vaccine efficacy which is also influenced by the selection of a proper administration route. Co-delivery of multiple mRNAs enables synergistic effects and further enhances immunity in some cases. In this chapter, we overview the recent progress and existing challenges in the formulation and delivery technologies of mRNA vaccines with perspectives for future development.
| S-EPMC8195316 | biostudies-literature
Project description:mRNA is increasingly being recognized as a promising alternative to pDNA in gene vaccinations. Only recently, owing to the needs of cancer immunotherapies, has the biomaterials/gene delivery community begun to develop new biomaterial strategies for immunomodulation. Here, we report a novel way to use implantable porous scaffolds as a local gene delivery depot to enhance mRNA vaccine immunization in vitro, and in vivo when compared with conventional bolus injections. We first evaluated transfection efficiencies of single-stranded mRNA condensed and charge neutralized with two lipids (Lipofectamine Messenger MAXTM LM-MM and StemfectTM SF) and two cationic polymers (in vivo-jetPEI™, Poly (?-amino ester)) as gene carriers. As SF demonstrated highest in vitro transfection and cell viability, it was selected for subsequent porous polymer scaffold-loading trials. Enhanced in vitro transfection of SF:mRNA nanoparticle-loaded poly (2-hydroxyethyl methacrylate) (pHEMA) scaffolds was also observed with a DC2.4 cell line. Improved sustained local release and local transgene expression were also demonstrated with SF:mRNA nanoparticle-loaded pHEMA scaffolds in vivo compared with bolus injections. Our results suggest that mRNA polyplex-loaded scaffolds may be a superior alternative to either repeated bolus immunizations or ex vivo transfection cell immunotherapies.
| S-EPMC6309225 | biostudies-literature
Project description:Nucleic acid vaccines are a method of immunization aiming to elicit immune responses akin to live attenuated vaccines. In this method, DNA or messenger RNA (mRNA) sequences are delivered to the body to generate proteins, which mimic disease antigens to stimulate the immune response. Advantages of nucleic acid vaccines include stimulation of both cell-mediated and humoral immunity, ease of design, rapid adaptability to changing pathogen strains, and customizable multiantigen vaccines. To combat the SARS-CoV-2 pandemic, and many other diseases, nucleic acid vaccines appear to be a promising method. However, aid is needed in delivering the fragile DNA/mRNA payload. Many delivery strategies have been developed to elicit effective immune stimulation, yet no nucleic acid vaccine has been FDA-approved for human use. Nanoparticles (NPs) are one of the top candidates to mediate successful DNA/mRNA vaccine delivery due to their unique properties, including unlimited possibilities for formulations, protective capacity, simultaneous loading, and delivery potential of multiple DNA/mRNA vaccines. This review will summarize the many varieties of novel NP formulations for DNA and mRNA vaccine delivery as well as give the reader a brief synopsis of NP vaccine clinical trials. Finally, the future perspectives and challenges for NP-mediated nucleic acid vaccines will be explored.
| S-EPMC7995055 | biostudies-literature
Project description:There has been increased interest in the development of RNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies. Rapid and cost-effective manufacturing methods in addition to potent immune responses observed in preclinical and clinical studies have made mRNA-based vaccines promising alternatives to conventional vaccine technologies. However, efficient delivery of these vaccines requires that the mRNA be protected against extracellular degradation. Lipid nanoparticles (LNPs) have been extensively studied as non-viral vectors for the delivery of mRNA to target cells because of their relatively easy and scalable manufacturing processes. This review highlights key advances in the development of LNPs and reviews the application of mRNA-based vaccines formulated in LNPs for use against infectious diseases and cancer.
| S-EPMC7913163 | biostudies-literature
Project description:Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines are being evaluated in clinical trials as prophylactic and therapeutic vaccines. However, until recently, their development has been limited by their instability and inefficient in vivo transfection. The nanodelivery system plays a dual function in RNA-based vaccination by acting as a carrier system and as an adjuvant. That is due to its similarity to microorganisms structurally and size-wise; the nanodelivery system can augment the response by the immune system via simulating the natural infection process. Nanodelivery systems allow non-invasive mucosal administration, targeted immune cell delivery, and controlled delivery, reducing the need for multiple administrations. They also allow co-encapsulating with immunostimulators to improve the overall adjuvant capacity. The aim of this review is to discuss the recent developments and applications of biodegradable nanodelivery systems that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases.
| S-EPMC7823281 | biostudies-literature
Project description:In the past few years, there has been increasing focus on the use of messenger RNA (mRNA) as a new therapeutic modality. Current clinical efforts encompassing mRNA-based drugs are directed toward infectious disease vaccines, cancer immunotherapies, therapeutic protein replacement therapies, and treatment of genetic diseases. However, challenges that impede the successful translation of these molecules into drugs are that (i) mRNA is a very large molecule, (ii) it is intrinsically unstable and prone to degradation by nucleases, and (iii) it activates the immune system. Although some of these challenges have been partially solved by means of chemical modification of the mRNA, intracellular delivery of mRNA still represents a major hurdle. The clinical translation of mRNA-based therapeutics requires delivery technologies that can ensure stabilization of mRNA under physiological conditions. Here, we (i) review opportunities and challenges in the delivery of mRNA-based therapeutics with a focus on non-viral delivery systems, (ii) present the clinical status of mRNA vaccines, and (iii) highlight perspectives on the future of this promising new type of medicine.
| S-EPMC7076378 | biostudies-literature