mRNA is the minimal genetic vector therefore, anti-vector immunity is avoided, and mRNA vaccines can be administered repeatedly. Efficient in vivo delivery can be achieved by formulating mRNA into carrier molecules, allowing rapid uptake and expression in the cytoplasm (reviewed in REFS 10, 11). Second, efficacy: various modifications make mRNA more stable and highly translatable 9, 12, 13. The inherent immunogenicity of the mRNA can be down-modulated to further increase the safety profile 9, 12, 13. Additionally, mRNA is degraded by normal cellular processes, and its in vivo half-life can be regulated through the use of various modifications and delivery methods 9– 12. First, safety: as mRNA is a non-infectious, non-integrating platform, there is no potential risk of infection or insertional mutagenesis. The use of mRNA has several beneficial features over subunit, killed and live attenuated virus, as well as DNA-based vaccines. Over the past decade, major technological innovation and research investment have enabled mRNA to become a promising therapeutic tool in the fields of vaccine development and protein replacement therapy. Instead, the field pursued DNA-based and protein-based therapeutic approaches 7, 8. However, these early promising results did not lead to substantial investment in developing mRNA therapeutics, largely owing to concerns associated with mRNA instability, high innate immunogenicity and inefficient in vivo delivery. A subsequent study in 1992 demonstrated that administration of vasopressin-encoding mRNA in the hypothalamus could elicit a physiological response in rats 6. The first report of the successful use of in vitro transcribed (IVT) mRNA in animals was published in 1990, when reporter gene mRNAs were injected into mice and protein production was detected 5. Nucleic acid therapeutics have emerged as promising alternatives to conventional vaccine approaches. The development of more potent and versatile vaccine platforms is therefore urgently needed. Finally, conventional vaccine approaches may not be applicable to non-infectious diseases, such as cancer. Moreover, for most emerging virus vaccines, the main obstacle is not the effectiveness of conventional approaches but the need for more rapid development and large-scale deployment. Despite this success, there remain major hurdles to vaccine development against a variety of infectious pathogens, especially those better able to evade the adaptive immune response 4. Conventional vaccine approaches, such as live attenuated and inactivated pathogens and subunit vaccines, provide durable protection against a variety of dangerous diseases 3. As a result of widespread vaccine use, the smallpox virus has been completely eradicated and the incidence of polio, measles and other childhood diseases has been drastically reduced around the world 2. Vaccines prevent many millions of illnesses and save numerous lives every year 1.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |