MRNA therapy effective treatment of rare hereditary diseases

Abstract

mRNA therapy, or mRNA-based drugs that have emerged thanks to vaccines against SARS-CoV-2, have successfully passed preclinical tests and are currently at various stages of clinical trials in the treatment of many diseases, including rare metabolic disorders. In the case of rare genetic metabolic diseases, the concept of mRNA therapy can be considered as an alternative to protein replacement therapy, where exogenous mRNA leads to the production of a fully active protein instead of a non-functional one, and also delivers it to the desired cellular compartment, such as mitochondria or the cell membrane. Preclinical studies on animal models of some rare genetic diseases have fully confrmed the validity of this concept. In this mini-review, we examine and discuss the mentioned preclinical studies on efficacy and safety in several animal models. For all the diseases considered, mRNA therapy restored functional protein to therapeutically significant levels in target organs, led to stable and reproducible results after each dose of mRNA, and was well tolerated, as confirmed by functional liver tests evaluated in animal models, including non-human primates. These data convincingly confirm the potential of clinical development of mRNA therapy for the treatment of various rare metabolic disorders.