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Using gene therapy to combat HBV infection

- Wits University

Hepatitis B Virus causes between 600 000 and one million deaths per year, predominantly in sub-Saharan Africa and Asia.

Dr Buhle Moyo, a postdoctoral research fellow in the Department of Molecular Haematology at Wits, is working towards the development of safe and effective gene therapeutics against the Hepatitis B Virus (HBV).

Moyo joined the Antiviral Gene Therapy Research Unit (AGTRU) in 2013 and her research focuses on using a re-engineered virus to deliver a therapeutic gene to the liver, the site of HBV infection.

HBV causes liver cancer and cirrhosis and causes between 600 000 and one million deaths per year, predominantly in sub-Saharan Africa and Asia.

Gene therapy technologies offer potential solutions for the effective management of intractable diseases and intensive research activities are underway to apply these technologies to HBV infection.

The AGTRU has developed a number of highly efficacious gene therapeutics capable of interfering with the life cycle of HBV. However, the biggest hurdle facing implementation of gene therapeutics in a clinical setting is the lack of an effective means of delivering the therapy to the target organ.”

The problem was that we needed to find a system to deliver the gene therapy safely and efficiently,” says Moyo.

“We’ve been working with using Adeno-Associated Viruses (AAVs) as a vector and we were able to re-engineer it successfully.”

AAVs are small viruses that infect humans. They are not known to cause disease and they are able to efficiently deliver their cargo and are easy to re-engineer. As a consequence, AAVs are commonly used in the field of gene therapy.

The AGTRU recently described the successful adaptation of a novel technology, Transcription Activator-Like Effector Nucleases (TALENs), to disable HBV.

The work was published in Molecular Therapy, the official journal of the American Society of Gene and Cell Therapy, in 2013. These TALENs were engineered to bind and cut HBV DNA. Subsequent introduction of mutations at the cut site effectively disables the virus.

Moyo and the AGTRU team found AAVs are efficient vectors to carry the TALE-based therapies to the livers of mice.

The team is currently engaged in pre-clinical studies in mice to assess the efficacy of the delivery system and the gene therapeutics.

“We were able to show very effective delivery of the TALENs and have very promising results.  We are hoping to publish the results in a high-impact journal before the end of the year,” says Moyo.

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