Recombinant Adeno-Associated Virus-Mediated Gene Therapy for Treatment of Familial Hypercholesterolemia in Rabbits

Familial hypercholesterolemia (FH) is a genetic disorder characterized by abnormally high concentrations of low-density lipoprotein-cholesterol (LDLcholesterol) in the blood that can contribute to heart disease. FH can result from a defect in the gene for the LDL receptor (LDL-R). FH patients lacking functional LDL-R may benefit from viral-mediated transfer of a functional copy of the open reading frame (ORF) of the LDL-R. Since a recombinant adeno-associated virus (rAAV) is not immunogenic and can be mass-produced, it shows promise for gene therapy applications. AAV6 and AAV8 have been shown to specifically transduce hepatocytes in several species, which normally remove the majority of LDL-cholesterol from the blood via LDL-R-mediated endocytosis. Because of the potential of rAAV to treat FH by delivery of a correct LDL-R ORF to hepatocytes, the liver specificity of these two AAV serotypes was evaluated. Additionally, rabbits were chosen as the animal model for this study because a specific strain of rabbits, Watanabe heritable hyperlipidemic (WHHL), adequately mimics the pathology of FH in humans. Exposure of rabbit liver to rAAV with the marker LacZ and subsequent inspection of liver tissue showed that AAV8 transduced rabbit liver more efficiently than AAV6. To assess the feasibility of producing a rAAV capable of transferring the LDL-R ORF to rabbit hepatocytes in vivo, rAAV8-LDL-R was mass-produced by a baculovirus system in suspension grown insect cells

Wolbachia in Dengue Control: A Systematic Review

BACKGROUND: Dengue fever outbreaks have been an important public health issue causing high morbidity and mortality, and serious economic effects, particularly in Asia. Control strategies are a challenge to be implemented due to a variety of factors. However, new approaches such as Wolbachia-infected Aedes aegypti have been shown to successfully lowering the life spans of the mosquito, eggs resistance, and disease transmission capabilities. Field trials are still on-going, and there are data to support its benefit in a large population. This systematic review aims to determine the current progress and impact of using Wolbachia in curbing dengue cases in high dengue case locations worldwide. METHODOLOGY: The study uses the Preferred Reporting Items for Systematic reviews and Meta-Analyses review protocol, while the formulation of the research question was based on population of interest, comparison, and outcome. The selected databases include Web of Science, Scopus, PubMed, SAGE, and EBSCOhost. A thorough identification, screening, and included process were done and the results retrieved four articles. These articles were then ranked based on quality using mixed methods appraisal tool. RESULTS: A total of four articles were included from 2019 and 2020 reports in both dengue- and non-dengue-endemic settings. In this review, comparisons in terms of the hierarchy of the study design, community engagement and acceptance, Wolbachia-infected A. aegypti deployment, entomological outcome, and epidemiological outcomes were detailed. All four studies showed a decrease in dengue incidence in Wolbachia-intervention populations. CONCLUSION: Wolbachia programs have been shown to be an effective method in combating dengue diseases. Strong community engagement and involvement from multidisciplinary teams are important factors to ensure the effectiveness and good outcomes of the program