Browsing by Author "Arbuthnot, Patrick"

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    Long-term inhibition of Hepatitis B virus gene expression by a primary microrna expressing ancestral adeno-associated viral vector
    (BioMed Central, 2025-02) Mnyandu, Njabulo Ziphezinhle; Limani, Shonisani Wendy; Ely, Abdullah; Arbuthnot, Patrick; Maepa, Mohube Betty; Wadee, Reubina
    Current treatments for chronic infection with the hepatitis B virus (HBV) rarely cure carriers from the disease. Previously reported use of serotype 8 adeno-associated viral (AAV8) vectors to deliver expression cassettes encoding anti-HBV artificial primary microRNAs (apri-miRs) has shown promise in preclinical studies. A recently designed synthetic ancestral AAV (Anc80L65) with high liver transduction efficiency is a promising new addition to the anti-HBV vector toolbox. This study engineered Anc80L65 to express HBx-targeting apri-miRs. Single dose administration of the vectors to cultured cells and HBV transgenic mice effected reductions of secreted HBV surface antigen (HBsAg). Circulating HBV particles and HBV core antigen (HBcAg) were also significantly diminished in mice receiving the anti-HBV apri-miR-expressing ancestral AAVs. Downregulation of HBV biomarkers occurred over a period of 12 months. Absence of inflammatory responses or liver toxicity indicated that the vectors had a good safety profile. These data suggest that a single dose of apri-miR-expressing Anc80L65 is safe and capable of mediating durable suppression of HBV gene expression. Targeting HBx, which is required for transcriptional activity of covalently closed circular DNA of HBV, makes this Anc80L65-derived vector a promising candidate for functional cure from chronic HBV infection.
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    The Potential of Gene Therapy
    (University of the Witwatersrand, Johannesburg, 2011-06) Arbuthnot, Patrick
    Science of course has a lot to offer the public and effectively communicating the usefulness of science is very important. Scientists researching topics in the health-related fields have valuable practical benefits as a result of creation of interventions, methods, or strategies to treat disease. Moreover, the scientific method has a social function that is useful to nurture an ethic that encourages critical and creative thinking. This presentation is therefore primarily aimed at conveying insights about gene therapy to people who do not have a background in biology or medicine. The topic of gene therapy is rather technical in nature and I am therefore obliged to simplify some of the complex concepts. Also, parts of the talk will necessarily be of a didactic nature, which is important to provide the framework for discussing general issues of the significance of gene therapy in South Africa. The content of this presentation will be divided into 5 main parts, which are: Why genes are important in normal and disease biology; What is gene therapy?; Using silencing techniques to counter hepatitis B virus infection; The Challenges and Relevance of gene therapy research.