mRNA-Based Therapy for Skin Diseases
Systemic delivery of synthetic mRNA can lead to unspecific uptake, thus fail to target desired cells. Therefore, local and targeted administration of synthetic mRNA is a promising approach to increase site-specific delivery and efficiency, such as intradermal administration. Creative Biogene is your reliable and professional partner in mRNA research areas. We are offering a wide series of mRNA research services, including mRNA design, synthesis, purification of mRNA, and mRNA quality control services. We continuously challenge ourselves and strive to offer our customers the finest service. Here, we give an overview of advancements in mRNA-based protein replacement therapy in the skin.
mRNA-based therapy for skin diseases
Therapeutic mRNA is emerging as a new class of drugs with the improvements of research in molecular biology and biochemistry. The stability and immunogenicity of synthetic mRNA can be increased and modified through sequence optimization and chemical modifications. The combination of mRNA structural improvements and the development of safe and efficient mRNA delivery vehicles has paved the way for mRNA-based therapeutics. In addition to being tested in preclinical and clinical studies for a variety of diseases, such as oncology, infectious diseases, an emerging application of mRNAs is to supplement insufficient and defective proteins, also known as protein replacement therapy.
Intradermal delivery of synthetic mRNAs
Intradermal application of mRNA is a promising strategy to treat a variety of skin diseases or to promote wound healing by expressing desired proteins in the skin. Therefore, issues related to the systemically delivery of mRNA can be eliminated, including clearance from the bloodstream via the renal and hepatic systems. However, intradermal delivery of synthetic mRNAs also needs to overcome the skin barrier, stratum corneum (the outermost layer of the skin), which impedes the entry of topically applied drugs. To achieve successful delivery of synthetic mRNAs into the skin, a series of physical methods have been developed, including microneedles, jet injection, electroporation, and sonoporation. Through electric pulses or low-frequency ultrasound, electroporation and sonoporation allow instant skin penetration, introducing nucleic acid into the skin quickly and efficiently. However, electroporation and sonoporation need special equipment, which is related to high costs and limits autonomous use by patients. In addition, microneedles as one of the injections are being increasingly used for drug delivery. Unlike commonly used subcutaneous injection needles, microneedles do not reach the nerves and blood vessels of the dermis because of their short length. The use of microneedles not only warrants the reliable intradermal delivery of mRNA but also guarantees pain-free application as well as enhances patient compliance. Moreover, the method shows a significant dose sparing and can be used in vaccination against various infectious diseases for better immunogenicity.
Fig1. Delivery of synthetic hGLuc mRNA into porcine skin using hollow microneedles and analysis of protein expression. (Golombek, S., et al, 2018)
De novo synthesis of elastin by delivery of modified mRNA into skin
Due to aging, UV exposure or injury, elastin in the skin degrades, resulting in impaired elasticity and the formation of wrinkles as well as scarring. Elastin is one of the most important components of the skin, accounting for 2-3% of the dry weight of skin. As an extracellular matrix (ECM) protein, elastin provides elasticity and resilience to the skin. Although elastin is one of the most stable proteins known, elastin synthesis decreases from a young age and ceases in adults. A previous study had applied modified mRNA encoding tropoelastin (TE) for the de novo synthesis of elastin in vitro (human fibroblasts, EA.hy926 cells, and MSCs) and ex vivo (porcine skin). The delivered synthetic TE mRNA is able to produce elastin in elastin-deficient cells and in the skin (delivery of mRNA by microinjection). The study highlighted the auspicious mRNA-based integration-free method holds potential in the field of regenerative medicine to de novo elastin synthesis in the skin and other tissues.
If you have any requirements in this area, please don't hesitate to contact us. Creative Biogene is a leading service provider in mRNA-based drug research and development. Our extensive experience, an excellent team of experts, and advanced technology platforms make us an ideal partner for worldwide customers. We can support our customers with the most affordable, high-quality custom mRNAs according to the desired applications.
References
- Golombek, S., et al. (2018). "Intradermal delivery of synthetic mRNA using hollow microneedles for efficient and rapid production of exogenous proteins in skin." Molecular Therapy-Nucleic Acids, 11, 382-392.
- Lescan, M.,et al. (2018). "De novo synthesis of elastin by exogenous delivery of synthetic modified mRNA into skin and elastin-deficient cells." Molecular Therapy-Nucleic Acids, 11, 475-484.
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