Development of an antisense RNA delivery system using conjugates of the MS2 bacteriophage capsids and HIV-1 TAT cell-penetrating peptide.
RNA-based therapeutic strategies are used widely due to their highly specific mode of action. However, the major obstacle in any RNA-based therapy is cellular delivery and stability in the cells. The self-assembly of the MS2 bacteriophage capsids has been used to develop virus-like particles (VLPs) for drug delivery. In this study, we utilized the heterobifunctional crosslinker, sulfosuccinimidyl-4-(p-maleimidophenyl)-butyrate (sulfo-SMPB), to conjugate the human immunodeficiency virus-1 (HIV-1) Tat peptide and MS2 VLPs; the antisense RNA against the 5'-untranslated region (UTR) and the internal ribosome entry site (IRES) of the hepatitis C virus (HCV) was packaged into these particles by using a two-plasmid coexpression system. The MS2 VLPs conjugated with the Tat peptide were then transferred into Huh-7 cells containing an HCV reporter system. The packaged antisense RNA showed an inhibitory effect on the translation of HCV. This paper describes our initial results with this system using the Tat peptide.
Wei
Baojun
B
National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China.
Wei
Yuxiang
Y
Zhang
Kuo
K
Wang
Jing
J
Xu
Ruihuan
R
Zhan
Sien
S
Lin
Guigao
G
Wang
Wei
W
Liu
Min
M
Wang
Lunan
L
Zhang
Rui
R
Li
Jinming
J
D002213:Capsid; D036022:Capsid Proteins / Q000008:administration & dosage* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics; D006801:Humans; D017909:Levivirus / Q000648:ultrastructure*; D008113:Liver Neoplasms / Q000473:pathology; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D010446:Peptide Fragments / Q000008:administration & dosage*; D014176:Protein Biosynthesis / Q000187:drug effects; D016372:RNA, Antisense / Q000008:administration & dosage* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology; D012367:RNA, Viral / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053586:Virus Internalization; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage*
D036022:Capsid Proteins; D010446:Peptide Fragments; D016372:RNA, Antisense; D034741:RNA, Small Interfering; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; C497137:tat peptide (47-57), Human immunodeficiency virus 1; D008156:Luciferases