Cell and gene therapies are treatments that currently revolutionise medicine as they have the potential to cure serious and incurable diseases. In cell therapy, living cells from a patient or healthy donor are used to repair damaged tissue or boost the functioning of the immune system. Gene therapy aims to replace or repair defective genes with healthy ones in order to cure genetic diseases. Technologies for the development of cell and gene therapies center around gene transfer and genetic modification of cells. Today, there is enormous hope for these forms of advanced therapies, but major challenges in terms of safety, efficacy and production remain.

This article spotlights two emerging technologies for cell and gene therapy: mRNA technology and adeno-associated virus (AAV) technology.

I. mRNA-based Cell and Gene Therapies

mRNA-based therapies utilise the genetic information of messenger RNA (mRNA) to produce specific proteins within the patient’s cells. These proteins can serve various therapeutic functions, such as stimulating the immune response against diseases (such as in the well-known COVID-19 vaccines), replacing missing or defective proteins, or inhibiting the function of disease-causing proteins. One example, is the application of mRNA as a non-viral vector for the genetic modification of immune cells to transform them into cell therapeutics by introducing chimeric antigen receptors (CAR) as new surface receptors.

mRNA-based CAR-T Cells

Immune cells modified with new surface receptors, known as CAR-T cells, are clinically well-established cell therapies that are used to treat blood cancers that do not respond to any other treatment. All approved CAR-T cell therapies use lentiviral vectors for genetic transfer of the CAR into T cells. However, using lentiviral vectors the CAR gene is permanently integrated into the genome of the patient’s own immune cells. Using mRNA for this genetic modification instead of viral vectors has various advantages: ensuring temporal restriction of the CAR expression, allowing better control over immune activation and reducing potential side effects. In addition, it minimises the risk of insertional mutagenesis, a problem associated with DNA-based gene transfer, since mRNA does not integrate into the host cell’s DNA. This makes mRNA-based CAR-T cell therapy a promising and presumably safer approach for treating certain types of cancer and more recently also autoimmune diseases.