Poly(glycoamidoamine) Brushes Formulated Nanomaterials for Systemic siRNA and mRNA Delivery in Vivo

• Published in: Nano letters Vol. 16; no. 2; pp. 842 - 848
• Main Authors: Dong, Yizhou, Dorkin, J. Robert, Wang, Weiheng, Chang, Philip H, Webber, Matthew J, Tang, Benjamin C, Yang, Junghoon, Abutbul-Ionita, Inbal, Danino, Dganit, DeRosa, Frank, Heartlein, Michael, Langer, Robert, Anderson, Daniel G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10-02-2016
• Subjects: Animals; Brushes; Cytokines; Erythropoietin - antagonists & inhibitors; Erythropoietin - genetics; Factor VII - genetics; Gene Transfer Techniques; Genetic Therapy; Histology; Humans; Mice; Nanomaterials; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - adverse effects; Nanostructure; Polymers; RNA, Messenger - administration & dosage; RNA, Small Interfering - administration & dosage; Vehicles; nanomaterial; polymer brush; siRNA; mRNA; erythropoietin
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/acs.nanolett.5b02428

Safe and effective delivery is required for siRNA and mRNA-based therapeutics to reach their potential. Here, we report on the development of poly­(glycoamidoamine) brush nanoparticles as delivery vehicles for siRNA and mRNA. These polymers were capable of significant delivery of siRNA against FVII and mRNA-encoding erythropoietin (EPO) in mice. Importantly, these nanoparticles were well-tolerated at their effective dose based on analysis of tissue histology, systemic cytokine levels, and liver enzyme chemistry. The polymer brush nanoparticles reported here are promising for therapeutic applications.