A5010378353- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Hepatitis B Virus Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Viral gastroenteritis research and epidemiology
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- RNA Research and Splicing
- CAR-T cell therapy research
- Vibrio bacteria research studies
- RNA regulation and disease
- Bacteriophages and microbial interactions
- Cancer-related molecular mechanisms research
- Computational Drug Discovery Methods
- HIV Research and Treatment
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
Rice University
2019-2025
University of the Witwatersrand
2015-2017
South African Medical Research Council
2015-2017
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...
Genome-wide association studies typically identify hundreds to thousands of loci, many which harbor multiple independent peaks, each parsimoniously assumed be due the activity a single causal variant. Fine-mapping such variants has become priority and since most associations are located within regulatory regions, it is also that they colocalize with influence expression nearby genes. Here we examine these assumptions by using moderate throughput CROPseq protocol in Cas9 nuclease used induce...
Adeno-associated virus (AAV) is widely favored as a gene therapy vector, tested in over 200 clinical trials internationally. To improve targeted delivery variety of genetic capsid modifications, such insertion targeting proteins/peptides into the shell, have been explored with some success but larger insertions often unpredictable deleterious impacts on formation and delivery. Here, we demonstrate modular platform for integration exogenous peptides proteins onto AAV post-translationally...
Abstract Adeno-associated virus (AAV) has found immense success as a delivery system for gene therapy, yet the small 4.7 kb packaging capacity of AAV sharply limits scope its application. In addition, high doses are frequently required to facilitate therapeutic effects, leading acute toxicity issues. While dual and triple approaches have been developed mitigate problem, these necessitate even higher ensure that co-infection occurs at sufficient frequency. To address challenges, we herein...
Hepatitis B virus (HBV) infection is hyper-endemic (>8 % chronic carriers) to parts of Asia and sub-Saharan Africa. Persistent HBV predisposes liver diseases such as cirrhosis hepatocellular carcinoma. Current anti-HBV therapies face several limitations. RNA interference-based lack the robustness specificity required for therapeutic effect while interferon-α nucleotide/side analogs function post-transcriptionally thus allow persistence covalently closed circular (cccDNA). cccDNA may persist...
Abstract Although adeno-associated virus (AAV) has enjoyed enormous success as a delivery modality for gene therapy, it continues to suffer from the high prevalence of preexisting neutralizing antibodies in human populations, limiting who can receive potentially life-saving treatments. In this regard, AAV therapies generally also must be administered single dose since develop patients virus. Strategies circumventing these issues remain limited. As novel solution, we employed...
Hepatitis B virus (HBV) is hyperendemic to sub-Saharan Africa where there are approximately 600 000 deaths per year associated with chronic HBV infection. may have long periods of dormancy in carriers the virus, which dependent on persistence nuclear replication intermediate covalently closed DNA (cccDNA). Current therapies, including nucleot(s)ide analogs, target actively transcribed virus. The cccDNA not cleared and act as a reservoir for re-initiation viral following treatment withdrawal....