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Targeted delivery of si RNA against hepatitis B virus by pre S1 peptide molecular ligand
Author(s) -
Huang Wenjuan,
Li Xia,
Yi Min,
Zhu Sufen,
Chen Weixian
Publication year - 2014
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12189
Subject(s) - hbsag , in vivo , hepatitis b virus , in vitro , virology , small interfering rna , microbiology and biotechnology , rna interference , transfection , virus , chemistry , biology , rna , gene , biochemistry
Aim For chronic hepatitis B virus ( HBV ) infection, the effects of current therapies are limited. RNA interference of virus‐specific genes has emerged as a potential antiviral mechanism. However, a suitable delivery vector is still to be developed. We studied a novel vector transferring siRNA targeting hepatic cells in vivo and in vitro in order to find a new way to cure HBV ‐related live diseases. Methods The preS1‐9Arg ligand was used to deliver siRNA to HepG 2 and to HepG 2 2.2.15 cells. To validate the antiviral efficacy in vivo , a HBV viremic animal model was established by s.c. inoculation of HepG 2 2.2.15 tumor cells in nude mice. The minimal retardation effect on the migration of siRNA was detected by gel electrophoresis to confirm the combination and the optimal ratio. Hepatitis B surface antigen ( HBsAg ) levels were detected by semiquantitatively enzyme‐linked immunosorbent assay RNA levels were quantified with quantitative real‐time polymerase chain reaction and protein levels were determined with immunoblots and immunohistochemistry. Results PreS1‐9Arg peptide strongly combined and transferred siRNA into HepG 2 cells. PreS1‐9Arg ‐ siRNA molecular conjugate effectively reduced the production of HBsAg and HBV DNA without liver toxicity in vitro and in vivo . Conclusion The results indicated that p reS1‐9Arg may be a potential novel vector to deliver siRNA targeting liver cells.