Design, Synthesis, and Proof-of-Concept Bioassay of an Encapsulated mRNA for Human Growth Hormone

Background: Human growth hormone (hGH) deficiency (GHD) is typically treated with daily injections of recombinant human growth hormone (rhGH), which do not fully replicate physiological secretion patterns. This study evaluates a novel approach using synthetic mRNA encoding hGH encapsulated in lipid nanoparticles (LNPs) and designated VTRC-01 to enable endogenous hormone production. Methods: VTRC-01 was administered intramuscularly to hypophysectomized (Hypox) prepubertal Wistar rats, and its efficacy was compared with rhGH. A cohort of healthy rats was included to assess anabolic effects and safety. Results: VTRC-01 stimulated longitudinal growth in both Hypox and healthy rats, achieving effects comparable to rhGH. Treatment induced a significant anabolic response that exceeded the basal growth rate of healthy controls. Conclusions: These findings provide proof-of-concept for hGH mRNA-based therapy as a promising alternative to rhGH. Further improvements in mRNA and LNP technologies are expected to enhance safe hormone production. These promising results underscore the potential of reprogramming via therapeutic mRNA the synthesis of key endocrine regulators (such as hGH) directly within the organism, offering for the first time a powerful pathway for the potential treatment for endocrine therapies targeting growth hormone deficiency.