Gene Therapy offers new hope to beat hepatitis B by muting its DNA
A new experimental gene-silencing therapy is offering hope for a functional cure for chronic hepatitis B by switching off the virus’s DNA without cutting it, researchers have reported.
Chronic hepatitis B affects about 240 million people worldwide and is currently managed with lifelong antivirals that keep the virus under control but do not cure it. The virus persists in liver cells as cccDNA and integrated fragments that produce proteins to evade the immune system.
Researchers led by John Marlowe at genetic medicines company nChroma Bio have designed a genetic package called CRMA-1001. The therapy includes a targeting guide RNA to find viral DNA and instructions for making a gene-silencing protein, wrapped in lipid nanoparticles.
Instead of cutting DNA like CRISPR-Cas9, the approach uses epigenome editing — attaching chemical tags called methyl groups to viral DNA that act like a mute button, keeping the virus switched off without altering the underlying genetic code.
In preclinical studies, a single dose of the therapy reduced both levels of viral DNA and hepatitis B markers in human liver cells and mouse models. In one study, 25 of 60 mice showed undetectable viral levels for more than six months. Safety testing in macaques showed minimal and temporary adverse effects.
The researchers said the long-term goal is a single-administration gene silencer that can achieve lasting functional cure and free patients from lifelong antivirals. Human trials are expected to begin in January in Hong Kong and New Zealand.
The development comes as the US FDA on October 20 approved Hibsago (bepirovirsen), the first antisense oligonucleotide for chronic hepatitis B, which also targets viral genetic instructions.
