Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Pisa, Pisa, Italy.
PLoS One. 2019 Oct 23;14(10):e0224072. doi: 10.1371/journal.pone.0224072. eCollection 2019.
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.
信使 RNA（mRNA）和 microRNA（miRNA）为基础的治疗方法由于在制造、可扩展性和成本方面的最新进展，已成为基于 DNA 的治疗方法的有吸引力的替代品。此外，由于不存在诱导基因组变化的风险，以及由于 RNA 为基础的治疗方法的瞬时性质，潜在的不良反应将是暂时的，因此 RNA 为基础的治疗方法被认为是安全的。然而，RNA 为基础的治疗方法的有效体内递送仍然是一个挑战。我们通过利用包膜病毒的物理化学性质开发了一种 RNA 为基础的治疗方法的递送平台。通过将阳离子脂质体/RNA 复合物物理附着到痘苗病毒的病毒包膜上，我们能够将 mRNA、自我复制的 RNA 以及 miRNA 递送到靶细胞内。此外，我们还表明，这个名为 viRNA 平台的平台可以有效地将功能性 miRNA 模拟物递送到体内的 B16.OVA 肿瘤中。
