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An HBV viral particle infects a liver cell by binding the NTCP (sodium/bile acid co-transporting peptide) receptor. The core parts of the virus are then transported into the nucleus. ~ 10% of HBV DNA integrates into the host's chromosomes. However the remainder gets converted into an HBV-specific structure called HBV cccDNA (covalently closed circular DNA). cccDNA serves as a never-ending and untouchable source of HBV. One can think of cccDNA as a "blueprint" to making many more HBV "houses". A true cure requires elimination of HBV cccDNA from infected liver cells.  

HBx is one of seven proteins coded by HBV and may be the most exciting potential target for a cure because it has a central role in regulating cccDNA by allowing the unwinding (opening up) and thus expression of cccDNA. If HBx is inhibited, then cccDNA cannot be expressed and the virus cannot continue to replicate. Our cure, Hepativir-B, would be the equivalent to permanently shredding and locking up the "blueprints" so no more HBV "houses" can be built.  

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The reason why CRISPR-Cas9 technology is necessary to inhibit HBx is because it is challenging to make traditional drugs (such as small molecule chemicals or antibody biologics) against this intracellular protein which lacks a known enzymatic function. Therefore using a nuclease technology to inhibit HBx within the HBV genome (either integrated into the host chromosome or as part of cccDNA) is a promising approach.  Another advantage of CRISPR-Cas9 is one can easily inhibit a second target such as NTCP by simply dosing a "cocktail" of CRISPR-Cas9s to both targets (HBx and NTCP). By also targeting NTCP, Hepativir-B has two shots to thwart HBV. Blocking NTCP will prevent new liver cells from being infected by HBV viral particles that may be circulating in the patient's bloodstream.

Why HBx? Why NTCP?
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