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      A new developing class of gene delivery: messenger RNA-based therapeutics

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          Abstract

          Gene therapy has long been held as having the potential to become a front line treatment for various genetic disorders.

          Abstract

          Gene therapy has long been held as having the potential to become a front line treatment for various genetic disorders. However, the direct delivery of nucleic acids to correct a genetic disorder has numerous limitations owing to the inability of naked nucleic acids (DNA and RNA) to traverse the cell membrane. Recently, messenger RNA (mRNA) based delivery has become a more attractive alternative to DNA due to the relatively easier transfection process, higher efficiency and safety profile. As with all gene therapies, the central challenge that remains is the efficient delivery of nucleic acids intracellularly. This review presents the recent progress in mRNA delivery, focusing on comparing the advantages and limitations of non-viral based delivery vectors.

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          RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates.

          Andreas Pichlmair, Oliver Schulz, Choon Ping Tan … (2006)
          Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). We showed that influenza A virus infection does not generate dsRNA and that RIG-I is activated by viral genomic single-stranded RNA (ssRNA) bearing 5'-phosphates. This is blocked by the influenza protein nonstructured protein 1 (NS1), which is found in a complex with RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and potential target of viral immune evasion and suggest that its ability to sense 5'-phosphorylated RNA evolved in the innate immune system as a means of discriminating between self and nonself.
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            Nonviral vectors for gene delivery.

            Meredith A. Mintzer, Eric Simanek (2009)
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              The contribution of vaccination to global health: past, present and future.

              Brian Greenwood (2014)
              Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.
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                Author and article information

                Journal
                Journal ID (publisher-id): BSICCH
                Title: Biomaterials Science
                Abbreviated Title: Biomater. Sci.
                Publisher: Royal Society of Chemistry (RSC)
                ISSN (Print): 2047-4830
                ISSN (Electronic): 2047-4849
                Publication date Created: 2017
                Publication date (Electronic): 2017
                Volume: 5
                Issue: 12
                Pages: 2381-2392
                Affiliations
                [1 ]School of Materials Science and Engineering
                [2 ]Tianjin University
                [3 ]Tianjin 300072
                [4 ]China
                [5 ]Charles Institute of Dermatology
                [6 ]School of Medicine
                [7 ]University College Dublin
                [8 ]Dublin 4
                [9 ]Ireland
                Article
                DOI: 10.1039/C7BM00712D
                PubMed ID: 29063914
                SO-VID: 64af3cf4-4a13-4b07-80ed-a28d92137172
                Copyright © © 2017
                License:

                http://rsc.li/journals-terms-of-use

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