January 6, 2021

mRNA Treatment: Will a mRNA vaccine alter any DNA?

Reviewing the Future Generation of Therapeutics

The mRNA treatment involves mRNA sequences that play an essential role in protein synthesis, helping direct the disease's target. It allows replacing a defective gene through substitution and integration of the correct genetic code in the genome.

RNA therapeutics are a class of medications based on ribonucleic acid (RNA). The main types are those based on messenger RNA (mRNA), antisense RNA (asRNA), RNA interference (RNAi), and RNA aptamers.

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Of the four types, mRNA-based therapy is the only type which is based on triggering synthesis of proteins within cells, making it particularly useful in vaccine development,and mRNA vaccines have been developed in 2020 for use in combating the SARS-CoV-2 global pandemic. Antisense RNA is complementary to coding mRNA and is used to trigger mRNA inactivation to prevent the mRNA from being used in protein translation. RNAi-based systems use a similar mechanism, and involve the use of both small interfering RNA (siRNA) and micro RNA (miRNA) to prevent mRNA translation. However, RNA aptamers are short, single stranded RNA molecules produced by directed evolution to bind to a variety of biomolecular targets with high affinity thereby affecting their normal in vivo activity.

RNA is synthesized from template DNA by RNA polymerase with messenger RNA (mRNA) serving as the intermediary biomolecule between DNA expression and protein translation. Because of its unique properties (such as its typically single-stranded nature and its 2' OH group) as well as its ability to adopt many different secondary/tertiary structures, bot coding and noncoding RNAs have attracted special attention in medicine. Research has begun to explore RNAs potential to be used for therapeutic benefit, and unique challenges have occurred during drug discovery and implementation of RNA therapeutics.

Applications

Cancer immunotherapy:

Recently, the new cancer immunotherapy, the combining of self-delivering RNA(sd-rxRNA) and adoptive cell transfer(ACT) therapy, was invented by RXi Pharmaceuticals and the Karolinska Institute. In this therapy, the sd-rxRNA eliminated the expression of immunosuppressive receptors and proteins in therapeutic immune cells so it improved the ability of immune cells to destroy the tumor cells.

Vaccines:

There are a few different types of IVT mRNA-based vaccine development for infectious diseases. One of the successful types is using self-amplifying IVT mRNA that has sequences of positive-stranded RNA viruses. It was originally developed for a flavivirus and it was workable with intradermal injection. One of the other ways is injecting a two-component vaccine which is containing an mRNA adjuvant and naked IVT mRNA encoding influenza hemagglutinin antigen only or in combination with neuraminidase encoding IVT mRNA.

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