Liver-specific Gene Delivery Using Engineered Virus-Like Particles of Hepatitis E Virus
| Autor: | Sung Min Kim, Dong Jun Park, Seung Kew Yoon, Eun Byul Lee, Byung-Yoon Kang, Jung Eun Choi, Wonhee Hur, Jung-Hee Kim, Gil Won Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
viruses lcsh:Medicine Gene delivery Spodoptera medicine.disease_cause Transfection Virus Article Cell Line 03 medical and health sciences 0302 clinical medicine Plasmid Hepatitis E virus medicine Sf9 Cells Animals Humans lcsh:Science Tropism Multidisciplinary Chemistry lcsh:R Gene Transfer Techniques Virion virus diseases digestive system diseases Cell biology 030104 developmental biology Capsid Liver Cell culture Organ Specificity lcsh:Q Genetic Engineering 030217 neurology & neurosurgery Plasmids |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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