Expression of squamous cell carcinoma antigen-1 in liver enhances the uptake of hepatitis B virus envelope-derived bio-nanocapsules in transgenic rats.
We previously developed the bio-nanocapsule, which consists of hepatitis B virus envelope L proteins. The bio-nanocapsule can be used to deliver genes and drugs specifically to the human liver-derived tissues in xenograft models, presumably by utilizing the human liver-specific mechanism of hepatitis B virus infection. The hepatitis B virus tropism is highly restricted to humans and higher primates. Thus, to evaluate the in vivo therapeutic effects of forthcoming bio-nanocapsule-based medicines, it will be crucial to develop an animal model whose liver is susceptible to both bio-nanocapsule and hepatitis B virus. In the present study, we aimed to establish a bio-nanocapsule-susceptible animal model using transgenic rats expressing squamous cell carcinoma antigen-1 (SCCA1), which has been proposed to be a receptor for hepatitis B virus, interacting with the hepatitis B virus envelope protein and enhancing the cellular uptake of hepatitis B virus. We show that the recombinant SCCA1 protein interacts directly with bio-nanocapsule and inhibits its attachment to the cultured human liver-derived cells. Furthermore, we have established a transgenic rat that specifically expresses SCCA1 in the liver and also demonstrate that the amount of bio-nanocapsule accumulated in the liver is significantly increased by the SCCA1 expression. Histological analysis suggests that bio-nanocapsule is preferentially incorporated into the SCCA1-expressing hepatocytes but not into macrophages, such as Küppfer cells, nor into endothelial cells. Therefore, this animal model is expected to be useful for the development of bio-nanocapsule-based medicines.
Kasuya
Takeshi
T
Department of Structural Molecular Biology, The Institute of Scientific and Industrial Research, Osaka University, Japan.
Nomura
Shintaro
S
Matsuzaki
Takashi
T
Jung
Joohee
J
Yamada
Tadanori
T
Tatematsu
Kenji
K
Okajima
Toshihide
T
Tanizawa
Katsuyuki
K
Kuroda
Shun'ichi
S
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006515:Hepatitis B virus / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000378:metabolism*; D053769:Nanocapsules / Q000627:therapeutic use* / Q000821:virology; D051381:Rats; D055647:Rats, Transgenic; D015843:Serpins / Q000378:metabolism*; D014018:Tissue Distribution; D014759:Viral Envelope Proteins / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000951:Antigens, Neoplasm; D053769:Nanocapsules; D015843:Serpins; D014759:Viral Envelope Proteins; C051072:squamous cell carcinoma-related antigen