Elastin production by mRNA technology for rejuvenation of aged skin.

Abstract

Elastin is a crucial component of elastic fibers, conferring mechanical elasticity and flexibility while facilitating cell interactions within skin tissue, thereby orchestrating the organized structure and damage repair of the extracellular matrix (ECM). Although elastin has a long half-life, its production ceases in adults. Damage to elastin caused by both intrinsic and extrinsic aging leads to an irreversible loss of skin elasticity, a hallmark of skin aging. mRNA technology combined with lipid nanoparticle (LNP)-based delivery systems offers a platform for the de novo synthesis of elastin. However, for regenerative therapeutic applications, mRNA-LNP must overcome the inherent immunogenicity and interference from the senescence-associated chronic inflammatory microenvironment, which may suppress mRNA translation efficiency and exacerbate the "inflammation-elastin deficiency-ECM loss" cycle. Here, mRNA encoding the elastin precursor tropoelastin (TE) was constructed and delivered to promote de novo elastogenesis, counteracting both UVB-induced photoaging and D-galactose-mimicked natural skin aging. This was achieved using LNP incorporating Timonacic, which enhances the translational efficiency of TE mRNA and ameliorates inflammatory responses. This strategy disrupts the intrinsic cycle of skin aging, thereby offering a potential therapeutic approach for skin rejuvenation.