A5018314425- RNA Interference and Gene Delivery
- Hepatitis B Virus Studies
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Hepatitis C virus research
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Viral Infections and Outbreaks Research
- Epigenetics and DNA Methylation
- Circular RNAs in diseases
- Liver physiology and pathology
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Viral-associated cancers and disorders
- Vibrio bacteria research studies
- Biomedical and Engineering Education
- Biotechnology and Related Fields
University of the Witwatersrand
2016-2025
South African Medical Research Council
2016-2025
Chronic hepatitis B virus (HBV) infection remains an important global health problem. Stability of the episomal covalently closed circular HBV DNA (cccDNA) is largely responsible for modest curative efficacy available therapy. Since licensed anti-HBV drugs have a post-transcriptional mechanism action, disabling cccDNA potentially therapeutic benefit. To develop this approach, we engineered mutagenic transcription activator-like effector nucleases (TALENs) that target four HBV-specific sites...
The use of RNA interference (RNAi) to inhibit gene expression is potentially applicable in the treatment viral infections such as hepatitis B virus (HBV) persistence. Although efficient HBV silencing by short hairpin (shRNA) expressed from polymerase (Pol) III promoters has been reported, constitutive high-level transcription may cause harmful side effects. Here, we report an approach that allows a Pol II promoter improve regulation RNAi effecters. [cytomegalovirus (CMV)] or (U6) cassettes...
Exploiting the RNA interference pathway has shown promise for developing novel and effective treatment of hepatitis B virus (HBV) infection. To advance this approach, we analyzed antiviral efficacy a panel 10 Pol III U6 promoter-encoded short hairpin RNAs (shRNAs) that target conserved sequences oncogenic HBx open reading frame. facilitate intracellular processing, shRNAs included mismatches in 25-bp stem region terminal loop miRNA-23. Two (shRNA 5 shRNA 6) showed knockdown HBV markers by...
Activating RNA interference to achieve specific gene silencing has shown promise for the development of RNA-based treatment chronic hepatitis B virus (HBV) infection. To further this approach, we assessed efficacy expressed long hairpin RNAs (lhRNAs) that target conserved HBx open reading frame HBV. As substrates Dicer, lhRNAs have potential generate multiple short interfering (siRNAs) enable simultaneous targeting different sites. Two U6 Pol III vectors were constructed encode anti-HBV with...
Management of infection with hepatitis B virus (HBV) remains a global health problem. Persistence stable covalently closed circular DNA (cccDNA) during HBV replication is responsible for modest curative efficacy currently licensed drugs. Novel gene editing technologies, such as those based on CRISPR/Cas9, provide the means permanently disabling cccDNA. However, efficient delivery antiviral sequences to infected hepatocytes challenging. A limiting factor large size encoding Cas9 from...
Available interventions for the management of chronic hepatitis B (hepB) exhibit limited efficacy and barriers to vaccination against virus (HBV) have hampered prophylaxis programmes. Development potent therapeutics capable functional cure hepB thus remains a relevant medical objective. RNA interference (RNAi) can be exploited effect specific silencing target genes through introduction sequences that mimic natural activators pathway. To achieve therapeutic effect, artificial primary...
HIV-1 infection continues to be a global health challenge and vaccine is urgently needed. Broadly neutralizing antibodies (bNAbs) are considered essential as they inhibit multiple strains, but difficult elicit by conventional immunization. In contrast, non-neutralizing that correlated with reduced risk of in the RV144 HIV trial relatively easy induce, responses not durable. To overcome these obstacles, adeno-associated virus (AAV) vectors were used provide long-term expression targeting V2...
Africa bears the highest burden of infectious diseases, yet continent is heavily reliant on First World countries for development and supply life-saving vaccines. The COVID-19 pandemic was a stark reminder Africa’s vaccine dependence since then great interest has been generated in establishing mRNA manufacturing capabilities African continent. Herein, we explore alphavirus-based self-amplifying RNAs (saRNAs) delivered by lipid nanoparticles (LNPs) as an alternative to conventional platform....
Achieving safe delivery of anti-hepatitis B virus (HBV) RNA interference (RNAi) effectors is an important objective this gene-silencing technology. Adenoviruses (Ads) have a natural tropism for the liver after systemic administration, and are useful expressed anti-HBV RNAi sequences. However, drawback Ad vectors diminished efficacy toxicity that results from stimulation innate adaptive immunity. To attenuate these effects we used monomethoxy polyethylene glycol-succinimidyl propionate...
Chronic infection with the hepatitis B virus (HBV) occurs in approximately 6% of world's population and carriers are at risk for complicating hepatocellular carcinoma. Current treatment options have limited efficacy chronic HBV is likely to remain a significant global medical problem many years come. Silencing gene expression by harnessing RNA interference (RNAi) presents an attractive option development novel effective anti agents. However, despite rapid progress, further refinement...
Research on applying RNA interference (RNAi) to counter HBV replication has led identification of potential therapeutic sequences. However, before clinical application liver-specific expression and efficient delivery these sequences remain an important objective. We recently reported short-term inhibition in vivo by using helper dependent adenoviral vectors (HD Ads) expressing anti-HBV from a constitutively active cytomegalovirus (CMV) promoter. To develop the use transcription regulatory...
Chronic infection with hepatitis B virus (HBV) remains a problem of global significance and improving available treatment is important to prevent life-threatening complications arising in persistently infected individuals. HBV susceptible silencing by exogenous artificial intermediates the RNA interference (RNAi) pathway. However, toxicity Pol III cassettes short duration effectors RNAi pathway may limit anti-HBV therapeutic utility. To advance RNAi-based gene silencing, mono- trimeric...
Chronic infection with hepatitis B virus (HBV) is a serious global health problem. Persistence of the occurs as result stability replication intermediate comprising covalently closed circular DNA (cccDNA). Development drugs that are capable disabling this cccDNA vital.To investigate an epigenetic approach to inactivating viral DNA, we engineered transcriptional repressors comprise HBV DNA-binding domain transcription activator like effectors (TALEs) and fused Krüppel Associated Box (KRAB)....