Prokaryotic Expression of a Novel Therapeutic recombinant transbody H2L2
Targeting Hepatitis B Virus core protein
Abstract
Background and Purpose Chronic Hepatitis B virus (CHB) infection is a
global burden for public health. Treatment methods such as interferon
and nucleoside analogues may effectively control viral infection but
cannot eliminate the virus due to their inability to remove viral
covalently closed circular DNA (cccDNA) inside host nuclear. The
persistence of cccDNA in the infected hepatocytes is a crucial obstacle
to antiviral therapies. For years, efforts had been undertaken to
understand the formation and regulation of HBV cccDNA. Natural core
antibodies were modified to target intracellular core proteins across
the membrane to achieve antiviral effect in several studies. However,
modified natural antibody had limits: 1) it was unstable inside cells;
2) it had strong immunogenicity; 3) lack of targeting. Experimental
approach and Key Results Therefore, we altered natural antibody into a
micro-transbody which has correct intracellular folding, stronger
affinity, and weaker immunogenicity to establish a new recombinant
transbody for the specific and efficient immune clearance of viruses in
hepatocytes. Immunofluorescence and immunohistochemistry were used to
verify the transmembrane and antigen-binding ability of our recombinant
transbody. Conclusions & Implications Taken together, we demonstrate a
recombinant transbody H2L2 with transmembrane and antigen-binding
activity expressed by E.coli in this study, which may be an encouraging
exploration of therapeutic strategies against hepatitis B infection
inside hepatocellular.