Rapid Production of Human VEGF-A following Intradermal Injection of Modified VEGF-A mRNA Demonstrated by Cutaneous Microdialysis in the Rabbit and Pig In Vivo.

Rapid Production of Human VEGF-A following Intradermal Injection of Modified VEGF-A mRNA Demonstrated by Cutaneous Microdialysis in the Rabbit and Pig In Vivo. Biomed Res Int. 2019;2019:3915851 Authors: Pehrsson S, Hölttä M, Linhardt G, Danielson RF, Carlsson L Abstract Chemically modified mRNA is a novel, highly efficient, biocompatible modality for therapeutic protein expression that may overcome the challenges and safety concerns with current gene therapy strategies. We explored the efficiency of intradermally injected modified VEGF-A165 mRNA (VEGF-A mRNA) formulated in a biocompatible citrate/saline buffer to locally produce human VEGF-A165 protein. Rabbits (n=4) and minipigs (n=3) were implanted with subcutaneous microdialysis probes close to the injection sites and interstitial-fluid samples and skin biopsies were analysed for production of VEGF-A protein over time for up to 8 hours. Three to 4 hours after the intradermal injection of VEGF-A mRNA, detectable levels of human VEGF-A protein were seen in the microdialysis eluates in both species. In the pig, the VEGF-A concentrations increased dose-dependently reaching a maximum 6 hours after dosing (62.7±28.4, 357.6±240.6, and 746.3±210.2 pg/mL following injection of 24, 120, and 600 μg VEGF-A mRNA, respectively). Likewise, in tissue biopsies harvested at study end (8 hours after VEGF-A mRNA injection), the content of VEGF-A protein increased dose-dependently. In contrast, ...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research