New gene therapy advance holds promise for the treatment of the global killer HBV

August 9, 2013, Wits University

The hepatitis B virus (HBV) kills between 600 000 and one million people a year globally, predominantly in sub-Saharan Africa and Asia. Life-threatening complications from HBV include liver cancer and cirrhosis.

On 25 July 2013, a significant advance in the use of a gene therapy approach to treating the was described in an article published in Molecular Therapy, the official journal of the American Society of Gene and Cell Therapy.

The advance is based on engineering of a new class of proteins called TALENs that can recognise and disable the DNA of the HBV. It is the result of 18 months of intensive collaborative research between the Antiviral Gene Therapy Research Unit (AGTRU) at Wits University and the Laboratory of Cell and Gene Therapy at the University Medical Centre in Freiburg, Germany.

Kristie Bloom, a PhD student who has recently completed her thesis at Wits, undertook this work as part of her degree. Bloom's research was carried out under the co-supervision of ProfessorGene Therapy Professor Patrick Arbuthnot, Kristie Bloom and Dr Abdullah Ely Patrick Arbuthnot and Dr Abdullah Ely, both from the AGTRU.

Describing the way TALENs work, Arbuthnot says: "One part of the protein specifically recognises the DNA of the HBV and another part acts as a cutting enzyme – it literally cuts the DNA of the HBV, and then introduces mutations at the exact site of cutting, resulting in the disabling of the viral DNA."

To transport the TALENs to the HBV-infected cells, the team encodes the TALENs on engineered DNA.

"What we have demonstrated so far is proof of principle that the TALENs are effective, and that this approach could be developed as a treatment for people who are chronically infected with the HBV and prevent the risk of cancer and ."

"However to be used as therapy, we will require vectors (carriers) that are capable of delivering the DNA to target liver cells. The focus of our current work is the engineering of viruses to serve as safe and efficient carriers of the TALEN-encoding DNA to ," Arbuthnot explains.

HBV immunisation became compulsory in South Africa in 1995, which effectively prevents HBV infection. The infection is declining as a result. "However, it is of little use to individuals who are already carriers of the virus," Arbuthnot explains. "We are also confronted with a situation in sub-Saharan Africa where up until recently only 5-8% of babies had been vaccinated against HBV. The Bill and Melinda Gates Foundation is making a significant contribution to improving this cover."

What is definite is that HBV will be with us for some time to come. The prognosis for patients who develop as a result of HBV infection is grave, and may set in anytime from the teens onwards. It is a particularly aggressive tumour and few patients survive beyond six months from the time of diagnosis of the cancer.

But the future for the treatment of HBV may be improved considerably as a result of breakthroughs like this one, which harness gene therapy techniques.

"The term 'gene therapy' was coined in the 1970s and refers to the use of procedures that are intended to treat or alleviate disease by genetically modifying the cells of a patient," Arbuthnot explains. "The approach has enormous potential as it may be used to repair damaged genes (from, for example, inherited diseases) or silencing 'rogue' genetic elements (for example of cancers and viruses) to restore the health of cells."

The major focus area of the AGTRU is to employ gene-disabling technology to develop treatments for the persistent viral infections of serious human diseases in South Africa, such as the hepatitis B virus (HBV) and the human immunodeficiency virus type 1 (HIV-1).

"It is critical that South Africa and South African scientists participate fully in this research to avoid reliance on expertise developed elsewhere in the world; to derive maximum benefit from this powerful new technology and to maintain a strong standing in the international research community.

"The South African government has committed to developing a knowledge-based economy, which is commendable and the work we do is in line with this."

The AGTRU was launched in 2002 and the past eight years have been a busy time for the unit with the creation of new knowledge, technology, patented intellectual property (IP) and postgraduate student training, which are essential for advancing gene therapy for viral infections.

An important focus of the research unit is to provide world-class medical science training for young South African scientists. Particular emphasis is being placed on ensuring the demographics of South Africa are represented in the composition of the research team. Collaboration with labs from all over the world is also key to create synergy from the pooling of resources.

"One gene therapy drug was licensed in Europe during late 2012 and several promising drug treatments are now in various stages of clinical testing. We would like to make rapid progress with advancing gene therapy for HBV but the timeline is difficult to predict," says Arbuthnot. Research on has gained considerable momentum and the coming years are likely to witness exciting and significant developments in the treatment of HBV infection.

Explore further: New drug stimulates immune system to kill infected cells in animal model of hepatitis B infection

More information: … /abs/mt2013170a.html

Related Stories

New drug stimulates immune system to kill infected cells in animal model of hepatitis B infection

April 26, 2013
A novel drug developed by Gilead Sciences and tested in an animal model at the Texas Biomedical Research Institute in San Antonio suppresses hepatitis B virus infection by stimulating the immune system and inducing loss of ...

Vitamin D deficiency may help spread of hepatitis B throughout liver

June 6, 2013
Researchers from Germany have found that low levels of vitamin D are associated with high levels of hepatitis B virus (HBV) replication. Findings published online in Hepatology, a journal of the American Association for the ...

Hepatitis B virus control: Identifying proteins in mutation management

June 25, 2013
(Medical Xpress)—Researchers at Kanazawa University Graduate School of Medical Science in Japan have determined how APOBEC proteins mediate hypermutations that inhibit viral replication. They also identify the host factor ...

Earlier treatment for young patients with chronic hepatitis B more effective in clearing virus

September 6, 2012
Scientists from A*STAR's Singapore Institute for Clinical Sciences (SICS), together with clinical collaborators from London , discovered for the first time that children and young patients with chronic Hepatitis B Virus infection ...

New research sheds light on the molecular mechanisms by which a virus contributes to cancer

August 29, 2012
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and is associated with exposure to hepatitis B virus (HBV). Patients carrying the virus have a 100-fold greater risk of developing HCC, ...

Adult antiviral drug effective in suppressing hepatitis B in teens

December 5, 2012
A recent clinical trial found that the adult antiviral drug, tenofovir disoproxil fumarate (tenofovir DF), is safe and effective in treating adolescents with hepatitis B virus (HBV). Trial results published in the December ...

Recommended for you

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Zika virus damages placenta, which may explain malformed babies

January 18, 2018
Though the Zika virus is widely known for a recent outbreak that caused children to be born with microencephaly, or having a small head, and other malformations, scientists have struggled to explain how the virus affects ...

Certain flu virus mutations may compensate for fitness costs of other mutations

January 18, 2018
Seasonal flu viruses continually undergo mutations that help them evade the human immune system, but some of these mutations can reduce a virus's potency. According to new research published in PLOS Pathogens, certain mutations ...

Study reveals how MRSA infection compromises lymphatic function

January 17, 2018
Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.