Advances in the delivery of RNA therapeutics: from concept to clinical reality

• Published in: Genome medicine Vol. 9; no. 1; p. 60
• Main Authors: Kaczmarek, James C, Kowalski, Piotr S, Anderson, Daniel G
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27.06.2017; BioMed Central; BMC
• Subjects: Antisense oligonucleotide; Antisense oligonucleotides; Antisense RNA; Cancer therapies; Clinical trial; Clinical trials; CRISPR; Dendritic cells; Deoxyribonucleic acid; Disease; DNA; Drug development; Drugs; Gene Editing; Gene expression; Gene therapy; Genetic Therapy - methods; Genome editing; Genomes; Genomics; Humans; Immune response; Immunosuppressive agents; Messenger RNA; Messenger RNA delivery; mRNA; Oligonucleotides, Antisense - therapeutic use; Polymers; Proteins; Review; Rheumatoid arthritis; RNA editing; RNA, Small Interfering - therapeutic use; siRNA; Vectors (Biology); CRISPR; Messenger RNA delivery; Gene editing; Clinical trial; Short interfering RNA delivery; Antisense oligonucleotide; Gene therapy; RNA nanoparticle; mRNA vaccine
• ISSN: 1756-994X; 1756-994X
• DOI: 10.1186/s13073-017-0450-0

The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.