Opportunities and Challenges in the Delivery of mRNA-Based Vaccines

Pharmaceutics, Journal Year: 2020, Volume and Issue: 12(2), P. 102 - 102

Published: Jan. 28, 2020

In the past few years, there has been increasing focus on 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, protein replacement therapies, and treatment genetic diseases. However, challenges that impede successful translation these molecules into (i) mRNA is very large molecule, (ii) it intrinsically unstable prone to degradation by nucleases, (iii) activates immune system. Although some have partially solved means chemical modification mRNA, intracellular delivery still represents major hurdle. The therapeutics requires technologies can ensure stabilization under physiological conditions. Here, we review opportunities in with non-viral systems, present status highlight perspectives future this promising type medicine.

Language: Английский

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Human papillomavirus vaccine against cervical cancer: Opportunity and challenge

Cancer Letters, Journal Year: 2019, Volume and Issue: 471, P. 88 - 102

Published: Dec. 5, 2019

Cervical cancer is one of the most common cancers threatening women's health, and persistent infection high-risk human papillomavirus (HPV) closely related to pathogenesis cervical many other cancers. The carcinogenesis a complex process from precancerous lesion cancer, which provides an excellent window for clinical prevention, diagnosis, treatment. However, despite various preventions treatments such as HPV screening, prophylactic vaccines, surgery, radiotherapy, chemotherapy, disease burden remains heavy worldwide. Currently, three types quadrivalent vaccine, bivalent new nonavalent are commercially available. Although these vaccines effective in protecting against 90% infection, they provide limited benefits eliminate pre-existing infections. Therefore, progress has been made development therapeutic vaccines. Therapeutic differ that aim stimulate cell-mediated immunity kill infected cells rather than neutralizing antibodies. This review aims at systematically covering progress, current status future prospects prevention treatment HPV-associated lesions laying foundations original vaccine.

Language: Английский

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Challenges of Storage and Stability of mRNA-Based COVID-19 Vaccines

Vaccines, Journal Year: 2021, Volume and Issue: 9(9), P. 1033 - 1033

Published: Sept. 17, 2021

In December 2019, a new and highly pathogenic coronavirus emerged—coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), quickly spread throughout the world. response to this global pandemic, few vaccines were allowed for emergency use, beginning in November 2020, of which mRNA-based Moderna (Moderna, Cambridge, MA, USA) BioNTech (BioTech, Mainz, Germany)/Pfizer (Pfizer, New York, NY, have been identified as most effective ones. The mRNA platform rapid development vaccines, but their use is limited ultracold storage requirements. Most resource-poor countries do not cold chain execute mass vaccination. Therefore, determining strategies increase stability relatively higher temperatures can be game changer address current pandemic upcoming waves. review, we summarized research enhance RNA vaccine delivery system.

Language: Английский

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Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges

Applied Biosafety, Journal Year: 2020, Volume and Issue: 25(1), P. 7 - 18

Published: Jan. 24, 2020

National Institutes of Health (NIH) defines gene therapy as an experimental technique that uses genes to treat or prevent disease. Although is a promising treatment option for number diseases (including inherited disorders, some types cancer, and certain viral infections), the remains risky still under study make sure it will be effective safe.

Language: Английский

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Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(8), P. 1619 - 1629

Published: Aug. 1, 2022

Language: Английский

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Self-Amplifying RNA Viruses as RNA Vaccines

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(14), P. 5130 - 5130

Published: July 20, 2020

Single-stranded RNA viruses such as alphaviruses, flaviviruses, measles and rhabdoviruses are characterized by their capacity of highly efficient self-amplification in host cells, which make them attractive vehicles for vaccine development. Particularly, alphaviruses flaviviruses can be administered recombinant particles, layered DNA/RNA plasmid vectors carrying the replicon even molecules. Self-amplifying viral have been used high level expression tumor antigens, immunization studies elicited strong cellular humoral immune responses animal models. Vaccination has provided protection against challenges with lethal doses pathogens cells. Moreover, clinical trials demonstrated safe application promising results rhabdovirus-based phase III on an Ebola virus vaccine. Preclinical applications self-amplifying proven development due to presence replicons, amplification cells will generate superior significantly reduced amounts delivered. The need novel vaccines become more evident global COVID-19 pandemic, further highlighted urgency challenging emerging diseases.

Language: Английский

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Oncolytic Viro-Immunotherapy: An Emerging Option in the Treatment of Gliomas

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 5, 2021

The prognosis of malignant gliomas remains poor, with median survival fewer than 20 months and a 5-year rate merely 5%. Their primary location in the central nervous system (CNS) its immunosuppressive environment little T cell infiltration has rendered cancer therapies mostly ineffective, breakthrough such as immune checkpoint inhibitors (ICIs) have shown limited benefit. However, tumor immunotherapy is developing rapidly can help overcome these obstacles. But for now, remain fatal short therapeutic options. Oncolytic virotherapy (OVT) unique antitumor wherein viruses selectively or preferentially kill cells, replicate spread through tumors while inducing responses. OVTs also recondition microenvironment improve efficacy other immunotherapies by escalating cells into tumors. Some penetrate blood-brain barrier (BBB) possess tropism CNS, enabling intravenous delivery. Despite potential displayed oncolytic (OVs), optimizing OVT proved challenging clinical development, marketing approvals been rare. In June 2021 however, genetically engineered OV based on herpes simplex virus-1 (G47Δ), teserpaturev got conditional time-limited approval treatment Japan. this review, we summarize current state OVT, synergistic effect combination well hurdles to successful use. We provide some suggestions challenges treating gliomas.

Language: Английский

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Transboundary Animal Diseases, an Overview of 17 Diseases with Potential for Global Spread and Serious Consequences

Animals, Journal Year: 2021, Volume and Issue: 11(7), P. 2039 - 2039

Published: July 8, 2021

Animals provide food and other critical resources to most of the global population. As such, diseases animals can cause dire consequences, especially disease with high rates morbidity or mortality. Transboundary animal (TADs) are highly contagious transmissible, epidemic diseases, potential spread rapidly across globe substantial socioeconomic public health consequences. threaten supply, reduce availability non-food products, loss human productivity life. Further, TADs result in consequences from costs control preventative measures, trade restrictions. A greater understanding transmission, spread, pathogenesis these is required. Further work also needed improve efficacy cost both diagnostics vaccines. This review aims give a broad overview 17 TADs, providing researchers veterinarians current, succinct resource salient details regarding significant diseases. For each disease, we synopsis its status, species geographic areas affected, summary vitro vivo research models, when available, information prevention treatment.

Language: Английский

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Between hope and reality: treatment of genetic diseases through nucleic acid-based drugs

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: April 23, 2024

Abstract Rare diseases (RD) affect a small number of people compared to the general population and are mostly genetic in origin. The first clinical signs often appear at birth or childhood, patients endure high levels pain progressive loss autonomy frequently associated with short life expectancy. Until recently, low prevalence RD gatekeeping delay their diagnosis have long hampered research. era nucleic acid (NA)-based therapies has revolutionized landscape treatment new hopes arise perspectives disease-modifying drugs development as some NA-based now entering stage. Herein, we review that were approved currently under investigation for RD. We also discuss recent structural improvements therapeutics delivery system, which overcome main limitations market expansion current approaches developed address endosomal escape issue. finally open discussion on ethical societal issues raise this technology terms regulatory approval sustainability production.

Language: Английский

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Emerging Concepts and Challenges in Rheumatoid Arthritis Gene Therapy

Biomedicines, Journal Year: 2020, Volume and Issue: 8(1), P. 9 - 9

Published: Jan. 9, 2020

Rheumatoid arthritis (RA) is a systemic inflammatory joint disease affecting about 1% of the population worldwide. Current treatment approaches do not ensure cure for every patient. Moreover, classical regimens are based on nontargeted immune suppression and have significant side effects. Biological has advanced considerably but efficacy specificity issues remain. Gene therapy one potential future directions RA therapy, which rapidly developing. Several gene trials done so far been moderate success, experimental genetics studies yielded novel targets. As result, arsenal tools keeps growing. Currently, both viral nonviral delivery systems used therapy. Herein, we review recent

Language: Английский

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