In vitro transcribed (IVT) mRNA is gaining momentum as a potential new drug class for induction of antigen-specific immunity especially in the field of immuno-oncology, but also as a starting material in cell therapy approaches for gene editing or immune therapy purposes. The concept behind using IVT mRNA as a drug is the transfer of a defined genetic message into the cells of a patient for the ultimate purpose of preventing or altering a particular disease state. At present, in vitro transcribed (IVT) mRNA is being explored both for ex vivo use through readministering transfected cells to a patient as an immunotherapy and for direct in vivo therapeutic delivery/vaccination.

Advantages of IVT mRNAs as therapeutic drugs:

• Suitable to encode for antibodies, antigens, cytokines and any other type of protein.
• Transient, with adaptable activity and half-life.
• Avoids genomic integration problems sometimes seen in gene therapy, potentially resulting in a better safety profile.
• Can be designed and optimized pharmacologically and immunologically, making it suitable for a broad range of applications.
• Fast manufacturability, making it an inexpensive and flexible therapeutic to produce.

These characteristics allow for rapid development of mRNA therapeutics that are broadly applicable for treatment of many diseases, including cancer, infectious diseases and rare diseases. The major therapeutic areas for which ITV mRNA are currently being explored are immunotherapeutics, protein-replacement therapies, regenerative medicine applications.

Fig1. Potential therapeutic applications of IVT mRNA.

• Cancer immunotherapy

Firstly, IVT mRNA encoding tumour-associated antigen or chimeric antigen receptor are transfected into dendritic/T cells ex vivo. Then, transfected cells carrying such mRNA-encoded receptors are able to recognize and kill tumour cells that express the target antigen. The transient nature of mRNA reduces the risk of unwanted side effects by the uncontrolled expansion of adoptively transferred immune cells. Thus, numerous clinical trials using ex vivo IVT mRNA-transfected dendritic/T cells were performed in patients with cancer.

• Protein-replacement therapies

The supplementation of proteins that are not expressed or are not functional, as well as the substitution of foreign proteins that activate or inhibit cellular pathways (for example, therapeutic antibodies), are the most obvious applications for IVT mRNA-based drugs. Several diseases are being studied in which the malfunctioning proteins are being replaced by the in vivo production of the therapeutic intracellular and secreted proteins from transfected IVT mRNA.

• Regenerative medicine

Cell phenotype and function can be modulated in vitro using nucleoside-modified IVT mRNA. The IVT mRNA was not only used to induce pluripotency but also to differentiate induced pluripotent stem cells (iPSCs).

Using mRNA as a drug opens up a breadth of opportunities to treat and prevent disease. IntegrateRNA has worked for years to build the industry's leading RNA technology platform and a world-class team. On this basis, we offer comprehensive services and products to accelerate your basic research, human disease research and drug discovery projects. If you have any questions or requirements, don't hesitate to contact us.