Proteins are the “workhorses” within cells responsible for metabolic processes, transport processes and structural elements. They are coded by genes on DNA and this code is transcribed into a message (messenger RNA or mRNA) within the cell nucleus. This mRNA then leaves the nucleus and is translated into the protein on ribosomes (Figure 1). Therapeutic mRNA is being developed as a new class of biological drug. Such therapeutic mRNA can address a wide range of different diseases as described below.
Vaccines: Messenger RNA can be used to express a viral protein(s) and elicit a strong protective immune response. Multiple mRNA vaccines are in clinical development with our partners, including Covid-19 vaccines.
Monoclonal antibodies: Recombinant monoclonal antibodies are widely used in medicine. The manufacturing of these complex proteins, however, is very difficult and expensive – and it takes a long time to develop new monoclonals for patients. By using mRNA, new monoclonal antibodies can be rapidly designed. When the therapeutic mRNA is administered to patients, they then synthesize the antibody within their own cells. This allows a new monoclonal antibody to be more rapidly and safely developed.
Genetic disease: Many genetic diseases are the result of a key protein not being correctly coded on the DNA, resulting in the protein not being made or being defective. Examples include haemophilia which results from a lack of certain clotting factors in the blood and cystic fibrosis where patients do not have a functional transmembrane conductance regulator in lung cells. Expression of a therapeutic mRNA to provide a functional copy of the missing or defective protein has the potential to correct the genetic disorder.
Gene Editing: Rather than providing an mRNA therapeutic that encodes the protein missing in patients with a genetic disease, another approach is to correct the underlying problem by editing the patient’s DNA. In this approach mRNA is used to express an enzyme which will target and correct the defective gene. Gene editing can be used either to “switch on” a defective gene or to “switch off” a gene which is causing disease.
Although therapeutic mRNA has the potential to address a wide range of diseases, these biological drugs are very easily degraded in the body and are also large polar molecules which are not able to enter cells by themselves. They therefore require a carrier to protect them after administration and to allow delivery to the cell cytoplasm where they can then be translated into the corresponding therapeutic protein. Acuitas has developed LNP systems that can protect mRNA and very efficiently deliver these drugs to where they are needed in the body. In both preclinical and clinical studies, Acuitas LNP have been shown to be safe and effective
