Modified mRNAs in the Cardiovascular System: A New Platform for Gene Therapy

• Published in: Molecular therapy Vol. 25; no. 6; pp. 1266 - 1268
• Main Author: Haddad, Georges E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07-06-2017; Elsevier Limited; American Society of Gene & Cell Therapy
• Subjects: Advantages; Cardiovascular system; Deoxyribonucleic acid; Design; DNA; Efficiency; Expression vectors; Gene expression; Gene therapy; Genomes; Heart; Immune system; Injection; Innate immunity; mRNA; Myocardium; Nanoparticles; Oligonucleotides; Plasmids; Ribonuclease; Sucrose; Toll-like receptors; Vectors (Biology)
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2017.05.011

[...]like all viral vectors, AAVs can only be administered once because they elicit neutralizing antibodies that preclude re-injection. [...]recently, non-viral vectors have centered on DNA plasmids and their derivatives (liposome-DNA complexes [lipoplexes] and polymer-DNA complexes [polyplexes]), oligonucleotides, and their analogs, either alone or in complexes. Even though such vectors are easy to produce, they have proven to be inefficient in transducing myocardium and can cause inflammation at the site of injection. mRNA formed synthetically has been used for gene transfer in vivo but is limited by poor transduction efficiency owing to activation of the innate immune system (via activation of Toll-like receptor 7/8) and rapid degradation by RNase. [...]the use of modRNAs in vivo seems to target a wide variety of cell types, and it will be important to design modRNAs that are cell specific by designing expression cassettes that take advantage of specific expression profiles within a specific cell type or organ.