Areas of Interest
Dr. Wu’s laboratory is involved in research in gene therapy of
liver diseases and creating novel animal models for studying
liver diseases. Dr. Wu’s laboratory has developed a protein base
carrier molecule that can deliver molecular reagents such as
genes and antisense DNA and RNA molecules specifically to liver
cells (1). The original liver-specific carrier molecule has been
used to deliver human albumin gene and human low density
lipoprotein receptor in animals deficient in albumin or LDLR
expression resulting in partially reversal of metabolic liver
diseases. The novel carrier protein has also been show to be
successful in delivering molecular agents for treatment of
acquired liver diseases such as Hepatitis B and hepatic fibrosis
(2).
Research in this area is now focused on modifying the liver
specific carrier protein to include elements that would enhance
the efficiency of delivery process so that molecular agents
taken into liver cells by this system can be rendered more
biologically active and thus more therapeutically effective (3).
The laboratory is in the process of characterizing a normal
rat with humanized liver. We have produced a rat with normal
immune system capable of hosting human liver cells in its liver.
The animal has been shown to be susceptible to human hepatitis B
viral infection (4). We are now studying the molecular
regulation of human Hepatitis C virus and its structure since
not much is know about either of the two areas of HCV viral
genome (5). We will use rats with humanized liver to develop a
rodent model of HCV infection and to use this model to test
novel HCV therapeutics.
Selected Publications
Wu CH, Walton CM, Wu GY. Targeted gene transfer to liver using
protein-DNA complexes. Methods Mol Med.;69:15-23 (2002).
Wu, C.H., Sapozhnikov, E., and Wu, G.Y.: Evaluation of
multicomponent non-viral vectors for liver directed gene
delivery. J. Drug Target. 10(2): 105-111 (2002).
Smith RM, Walton CM, Wu CH, Wu GY. Secondary structure and
hybridization accessibility of hepatitis C virus 3'-terminal
sequences.J Virol.;76(19):9563-74 (2002).
Wu, C.H., Ouyang, E.C., Walton, C.M. and Wu, G.Y.: Human
hepatocytes transplanted into genetically immunocompetent rats
are susceptible to infection by hepatitis B virus in situ. J.
Viral Hepatitis 8:111-119 (2001).
Wu, C.H., Walton, C.M., and Wu, G.Y.:Targted inhibition of
type I procollgen synthesis by antisense DNA oligonucleotides.
Gene Ther and Reg 1:193-205 (2000). |
