A5009352688- Mitochondrial Function and Pathology
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- RNA regulation and disease
- Hepatitis B Virus Studies
- Metabolism and Genetic Disorders
- Molecular Biology Techniques and Applications
- Cellular transport and secretion
- Viral gastroenteritis research and epidemiology
- Bacteriophages and microbial interactions
- Amyloidosis: Diagnosis, Treatment, Outcomes
Precision BioSciences (United States)
2021-2023
University of Miami
2022
Diseases caused by heteroplasmic mitochondrial DNA mutations have no effective treatment or cure. In recent years, editing enzymes were tested as tools to eliminate mutant mtDNA in cells and tissues. Mitochondrial-targeted restriction endonucleases, ZFNs, TALENs been successful shifting heteroplasmy, but they all drawbacks gene therapy reagents, including: large size, heterodimeric nature, inability distinguish single base changes, low flexibility effectiveness. Here we report the adaptation...
Persistence of chronic hepatitis B (CHB) is attributed to maintenance the intrahepatic pool viral covalently closed circular DNA (cccDNA), which serves as transcriptional template for all gene products required replication. Current nucleos(t)ide therapies CHB prevent virus production and spread but have no direct impact on cccDNA or expression genes. We describe a potential curative approach using highly specific engineered ARCUS nuclease (ARCUS-POL) targeting (HBV) genome. Transient...
Abstract Nuclease-mediated editing of heteroplasmic mitochondrial DNA (mtDNA) seeks to preferentially cleave and eliminate mutant mtDNA, leaving wild-type genomes repopulate the cell shift mtDNA heteroplasmy. Various technologies are available, but many suffer from limitations based on size and/or specificity. The use ARCUS nucleases, derived naturally occurring I- Cre I, avoids these pitfalls due their small size, single-component protein structure high specificity resulting a robust...
Mitochondrial DNA (mtDNA) is present in multiple copies and phenotypic consequences of mtDNA mutations depend on the mutant load surpassing a specific threshold. Additionally, changes copy number can impact mitochondrial ATP production, resulting disease. Therefore, precise determination heteroplasmy crucial to study diseases. However, current methods be imprecise, quantifying small either or challenging. We developed new approach measure using single digital PCR (dPCR) probe. This method...
Transthyretin amyloidosis (ATTR) is a progressive and fatal disease caused by transthyretin (TTR) amyloid fibril accumulation in tissues, which disrupts organ function. As the TTR protein primarily synthesized liver, liver transplantation can cure familial ATTR but not an option for predominant age-related wild-type ATTR. Approved treatment approaches include stabilizers RNA-interference therapeutic, these require regular re-administration. Gene editing could represent effective one-time...