User:RNA Therapist/sandbox

mRNA Therapeutics
=== The ability to deliver or express proteins in a patients is the cornerstone of biotechnology. There are three main methods to achieve this that have been used therapeutically are to administer one of the following three therapeutics to a patient: ===


 * 1) a protein manufactured by expressing recombinant DNA encoding the protein in a host cell inside an incubator (Recombinant Protein?)
 * 2) a viral vector or purified DNA to express the protein in the patient's cells (Gene Therapy)
 * 3) messenger RNA (mRNA) to express the protein in the patient cells (mRNA Therapeutics)

=== mRNA Therapeutics refers to the use of synthetic messenger RNA to express a particular protein in a person for therapeutics and vaccines. mRNA is an alternative approach to the older and more common approaches of using recombinant proteins directly and gene therapy. ===

=== It was not initially obvious that mRNA Therapeutics would have advantages over gene therapy, as gene therapy has the potential to last for months or years after a single dosing, while introducing mRNA into a cell is more transient (hours to weeks)[]. Also, early on, it was assumed that mRNA, which is highly sensitive to serum and cellular nucleases[], would be challenging to use as a therapeutic. However, in the 1997, it was proposed that mRNA Therapeutics could have advantages over gene therapy for certain applications[]. The then emerging liposome technologies could encapsulate mRNA protecting it from nucleases in bodily fluids [malone]. Once inside the cell, mRNA with a natural 5' G cap structure and poly A tail could be stable in the cytoplasm for many hours[]. While liposome encapsulated DNA delivered to the cytoplasm requires translocation to the nucleus and assembly into the cellular transcription machinery to be expressed into proteins, mRNA delivered by liposomes is translated directly in the cytoplasm where it is delivery by liposomes. In fact, primary cells are notoriously difficult to transfect with liposome encapsulated DNA, while mRNA transfection into primary cells with liposomes leads to uniform and robust expression[]. While gene therapy can be long term or permanent, this long term expression leads to safety concerns[], while mRNAs shorter term effects is inherently more safe and repeated dosing can used for longer term applications[]. Also gene therapy has the risk of insertional mutagenesis, which does not occur with mRNA therapy[]. Additionally, mRNA delivery (as with plasmid DNA delivery) does not require immunogenic vector proteins, which has led to adverse effects, including fatal immunogenic responses, and reduced efficacy with gene therapy viral vectors[]. Compared to using recombinantly manufactured proteins, mRNA and Gene Therapy can be used to express intracellular proteins like transcription factors, and proteins expressed by mRNA and Gene Therapy have natural post-transcriptional modifications and folding. ===