Harnessing therapeutic viruses as a delivery vehicle for RNA-based therapy

PLoS One. 2019 Oct 23;14(10):e0224072. doi: 10.1371/journal.pone.0224072. eCollection 2019.

Abstract

Messenger RNA (mRNA) and microRNA (miRNA)-based therapeutics have become attractive alternatives to DNA-based therapeutics due to recent advances in manufacture, scalability and cost. Also, RNA-based therapeutics are considered safe since there are no risk of inducing genomic changes as well as the potential adverse effects would be only temporary due to the transient nature of RNA-based therapeutics. However, efficient in vivo delivery of RNA-based therapeutics remains a challenge. We have developed a delivery platform for RNA-based therapeutics by exploiting the physicochemical properties of enveloped viruses. By physically attaching cationic liposome/RNA complexes onto the viral envelope of vaccinia virus, we were able to deliver mRNA, self-replicating RNA as well as miRNA inside target cells. Also, we showed that this platform, called viRNA platform, can efficiently deliver functional miRNA mimics into B16.OVA tumour in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Drug Delivery Systems*
  • Female
  • Genetic Therapy*
  • Humans
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Vaccinia virus / genetics*

Substances

  • MicroRNAs
  • RNA, Messenger

Grants and funding

The research leading to these results has received funding from the European Research Council under ERC-consolidator Grant (https://erc.europa.eu), Agreement n. 681219 (VC) and Academy of Finland (www.aka.fi) grand number 1317206 (EY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.