However, unpolished pDNA contains traces of bacterial genomic DNA and three forms of pDNA (supercoiled, relaxed circle or linear) in variable proportions. Manufacture of mRNA might thus appear to require more effort than manufacture of pDNA. 11 Hence, the preparation of pDNA is the first step in the production of mRNA. In addition, mRNA binds to pattern recognition receptors and mRNA vaccines may be designed to be self-adjuvanting, 9 a property which peptide- and protein-based vaccines lack.Īll in all, mRNA presents a promising, even if challenging, class of therapeutic molecules that has the potential to become the basis of a “disruptive technology.” 10 In the following we are casting light on what has to be considered when developing an mRNA-vaccine technology touching important topics such as mRNA manufacturing and quality, mRNA format and formulation as well as antigen/protein expression and immunological properties of mRNA-vaccines.įunctional synthetic mRNA may be obtained by in vitro transcription of a cDNA template, typically plasmid DNA (pDNA), using a bacteriophage RNA polymerase. In contrast to peptides, mRNA vaccines lack MHC haplotype restriction. In terms of efficacy, mRNA-based therapeutics profit from the fact that they do not need to cross the nuclear envelope as opposed to DNA. Since changes of the encoded protein just alter the sequence of the RNA molecule, leaving its physico-chemical characteristics largely unaffected, diverse products can be manufactured using the same established production process without any adjustment, saving time and reducing cost compared with other vaccine platforms. Any protein can be encoded and expressed by mRNA, in principle enabling the development of prophylactic and therapeutic vaccines fighting diseases as diverse as infections and cancer as well as protein replacement therapies. MRNA as the technological basis of therapeutics and vaccines is characterized by a great flexibility with respect to production and application. Finally, this lack of genomic integration in combination with mRNA being non-replicative as well as metabolically decaying within a few days 8 makes mRNA a merely transient carrier of information. Thus, potentially detrimental genomic integration is excluded. Moreover, while recombination between single-stranded RNA molecules may occur in rare cases, 6, 7 mRNA does not interact with the genome. 5 As the minimal genetic construct, it harbors only the elements directly required for expression of the encoded protein. Particularly compared with DNA as a therapeutic or more specifically as a vaccine, mRNA offers strong safety advantages. 2 Only a couple of years later, mRNA was advocated as a vaccine platform, perhaps being ideal in the sense that it brings together the immunological features of live attenuated vaccines such as endogenous antigen expression and T cell induction with those of killed or subunit vaccines like defined composition and safety. Despite the sensitivity of the molecule to the virtually omnipresent ribonucleases (RNases), 1 mRNA as a therapeutic was first promoted in 1989 after the development of a broadly applicable in vitro transfection technique. RNA is considered as notoriously unstable making its therapeutic use a provocative idea.
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |