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A cure in the making

- Wits University

An estimated 350 million people worldwide are infected with chronic Hepatitis B Virus (HBV) with the majority living in sub-Saharan Africa.

In South Africa, HBV infections are prevalent among Africans but it is rare in other racial groups.

While in many adults acute HBV infection does not require treatment as the infection is cleared spontaneously, PhD researcher Musa Donald Marimani is working on a possible cure for chronic HBV infections.

“Although an effective HBV vaccine has been used in South Africa since 1995, it is not beneficial to people that are chronically infected before being vaccinated. As such, development of effective HBV therapy remains a priority,” explains Marimani.

Currently, licensed HBV therapies act by inhibiting the formation of HBV DNA in hepatocytes (the cells that make up the majority of the cells in the liver) during viral replication or by activating the host’s immune system to combat the infection.

While these drugs suppress viral replication to reduce liver damage, they rarely clear the infection.

Marimani’s research involves introducing small interfering ribonucleic acid (siRNAs) as therapeutic agents into cultured mammalian cells and in HBV transgenic mice to prevent the replication of HBV.

The double stranded siRNA molecules containing single 2`-O-guanidinopropyl (GP)-modification were synthesised by Professor Joachim Engels from the Goethe University in Germany and tested for efficacy in human liver tumour cells. Similarly, siRNAs were mixed with liposomes synthesised by Professor Daniel Scherman at the Université Paris Descartes in France and tested in HBV transgenic mice.

Marimani’s research resulted in two key findings. The first is that the siRNAs were able to significantly reduce HBV replication in cultured cells without inducing toxicity or innate immune stimulation, thus prompting further efficacy studies in HBV transgenic mice.

Secondly, in these mice, GP-modified siRNAs significantly suppressed HBV replication for up to 14 days after single administration, without evidence of toxicity or innate immune stimulation, thus indicating the utility of GP-modified siRNAs in countering viral replication. These findings are useful for therapeutic application against chronic HBV infection.

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