A Superlong-Acting Growth Hormone-Polypeptide Fusion for Growth Hormone Deficiency Treatment

Recombinant human growth hormone (rhGH) is clinically used to treat growth hormone deficiency (GHD). However, daily administration of rhGH is required due to its poor stability and short blood circulation, which causes pains and burdens as well as inconvenience to patients. In this study, a method for genetically fusing rhGH to a thermosensitive polymer of elastin-like polypeptide (ELP) is reported, using which the rhGH-ELP thermosensitive fusion protein can be purified by the thermosensitivity of ELP instead of chromatography. The ELP fusion not only drastically improves the stability of rhGH, but also enables the in situ formation of a sustained-release depot of rhGH-ELP upon subcutaneous (SC) injection, which exhibits gentle release with a platform-to-trough fluctuation in blood and a very long circulatory half-life of 594.6 h. In contrast, rhGH exhibits a peak-to-trough fluctuation in blood with a very short circulatory half-life of 0.7 h. As a result, a single subcutaneous injection of rhGH-ELP can consecutively promote the linear growth of rats and the development of major tissues and organs over 3 weeks without obvious side effects, whereas rhGH is required to be injected daily to achieve similar therapeutic results. Recombinant human growth hormone (rhGH) is genetically fused to a thermosensitive biopolymer of elastin-like polypeptide (ELP) to yield a fusion protein of rhGH-ELP. The unique thermoresponsibility of rhGH-ELP enables the in situ formation of an injectable depot of rhGH-ELP with enhanced stability, sustained release, and improved pharmacokinetics for promotion of the body growth and development of rats.image

Automated summary

This study reports a method of genetically fusing recombinant human growth hormone (rhGH) to a thermosensitive elastin-like polypeptide (ELP), resulting in the formation of rhGH-ELP fusion protein. The fusion protein exhibits enhanced stability and sustained release, allowing for the promotion of linear growth and development in rats. This approach has the potential to reduce the frequency of rhGH administration and improve patient convenience.