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- Title
Liver-specific Gene Delivery Using Engineered Virus-Like Particles of Hepatitis E Virus.
- Authors
Lee, Eun Byul; Kim, Jung-Hee; Hur, Wonhee; Choi, Jung Eun; Kim, Sung Min; Park, Dong Jun; Kang, Byung-Yoon; Lee, Gil Won; Yoon, Seung Kew
- Abstract
Virus-like particles (VLPs) possess great potential for organ-specific transport of therapeutic agents due to their central cavity surrounded by viral capsid proteins and similar tropism to their original viruses. The N-terminal truncated second open reading frame (Nt-ORF2) of the hepatotropic hepatitis E virus (HEV) forms VLPs via self-assembly. In the present study, we investigated whether HEV-LPs could deliver foreign genes specifically to the liver. HEV-LPs were obtained from Nt-ORF2 expression in Huh7 cells that were transduced with recombinant baculoviruses and purified by continuous density gradient centrifugation. The purified HEV-LPs efficiently penetrated liver-derived cell lines and the liver tissues. To evaluate HEV-LPs as gene delivery tools, we encapsulated foreign plasmids in HEV-LPs with disassembly/reassembly systems. Green fluorescence was detected at higher frequency in liver-derived Huh7 cells treated with HEV-LPs bearing GFP-encoding plasmids than in control cells. Additionally, HEV-LPs bearing Bax-encoding plasmids induced apoptotic signatures in Huh7 cells. In conclusion, HEV-LPs produced in mammalian cells can encapsulate foreign genes in their central cavity and specifically transport these genes to liver-derived cells, where they are expressed. The present study could contribute to advances in liver-targeted gene therapy.
- Publication
Scientific Reports, 2019, Vol 9, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-019-38533-7