Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery

• Published in: Molecular therapy Vol. 27; no. 4; pp. 710 - 728
• Main Authors: Kowalski, Piotr S., Rudra, Arnab, Miao, Lei, Anderson, Daniel G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10-04-2019; Elsevier Limited; American Society of Gene & Cell Therapy
• Subjects: Animals; Biomaterials; Cell-Penetrating Peptides - chemistry; clinical trial; CRISPR; CRISPR-Cas Systems; Cytomegalovirus; Dendrimers - chemistry; Drug Delivery Systems - methods; gene editing; Gene Editing - methods; gene therapy; Genetic Therapy - methods; Genome editing; Humans; Immunization; lipid nanoparticles; Lipids; Lipids - chemistry; Mice; mRNA; mRNA delivery; mRNA nanoparticles; mRNA vaccine; Nanoparticles - chemistry; Polymers - chemistry; protein replacement; Review; RNA, Messenger - genetics; RNA, Messenger - therapeutic use; Skin cancer; Translation; Vaccination; Vaccination - methods; Zika virus; mRNA nanoparticles; clinical trial; CRISPR; lipid nanoparticles; gene therapy; mRNA delivery; biomaterials; gene editing; mRNA vaccine; protein replacement
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2019.02.012

mRNA has broad potential as a therapeutic. Current clinical efforts are focused on vaccination, protein replacement therapies, and treatment of genetic diseases. The clinical translation of mRNA therapeutics has been made possible through advances in the design of mRNA manufacturing and intracellular delivery methods. However, broad application of mRNA is still limited by the need for improved delivery systems. In this review, we discuss the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in biomaterials and delivery strategies, and we present an overview of the applications of mRNA-based delivery for protein therapy, gene editing, and vaccination.
This review addresses the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in biomaterials and delivery strategies, and the authors present an overview of the applications of mRNA-based delivery for protein therapy, gene editing, and vaccination.