A5034749831- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- Parvovirus B19 Infection Studies
- Herpesvirus Infections and Treatments
- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- Insect Pest Control Strategies
- Animal Virus Infections Studies
- Agricultural pest management studies
- Insect-Plant Interactions and Control
- Dermatological and COVID-19 studies
- Insect Resistance and Genetics
- Cytomegalovirus and herpesvirus research
- Insect and Pesticide Research
- interferon and immune responses
- DNA Repair Mechanisms
- Bacteriophages and microbial interactions
- Prenatal Screening and Diagnostics
- Blood groups and transfusion
- Agricultural Practices and Plant Genetics
- Biochemical and Molecular Research
- Ruminant Nutrition and Digestive Physiology
Florida College
2015-2024
University of Florida
2015-2024
PerkinElmer (United States)
2022
Indiana University School of Medicine
1997-2020
University of Florida Health
2008-2020
Indiana University – Purdue University Indianapolis
1996-2020
Institute for Stem Cell Biology and Regenerative Medicine
2020
Christian Medical College & Hospital
2020
Eli Lilly (United States)
2020
University of Alabama at Birmingham
2020
The complete nucleotide sequence of the adeno-associated virus 2 genome was determined. single-stranded is 4,675 nucleotides in length and contains inverted terminal repeats 145 nucleotides, first 125 which form a palindromic sequence. Within repetitions, there are two distinct sequences representing an inversion 43 that can exist on either terminus. 5' 3' termini three major mRNA transcripts, present both spliced unspliced forms, were also mapped viral genome. Potential initiation...
Recombinant adeno-associated virus 2 (AAV2) vectors are in use several Phase I/II clinical trials, but relatively large vector doses needed to achieve therapeutic benefits. Large also trigger an immune response as a significant fraction of the fails traffic efficiently nucleus and is targeted for degradation by host cell proteasome machinery. We have reported that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects transduction AAV2 impairing...
Vectors derived from adeno-associated viruses (AAVs) have become important gene delivery tools for the treatment of many inherited ocular diseases in well-characterized animal models. Previous studies determined that viral capsid plays an essential role cellular tropism and efficiency transgene expression. Recently, it was shown phosphorylation surface-exposed tyrosine residues AAV2 targets particles ubiquitination proteasome- mediated degradation, mutations these lead to highly efficient...
Vectors based on adeno-associated virus serotype 2 (AAV2) have been used extensively in many gene-delivery applications, including several successful clinical trials for one type of Leber congenital amaurosis the retina. Many studies focused improving AAV2 transduction efficiency and cellular specificity by genetically engineering its capsid. We previously shown that vectors-containing single-point mutations capsid surface tyrosines serotypes AAV2, AAV8, AAV9 displayed significantly...
Gene replacement therapy by in vivo delivery of adeno-associated virus (AAV) is attractive as a potential treatment for variety genetic disorders. However, while AAV has been used successfully many models, other experiments clinical trials and animal models have hampered undesired responses from the immune system. Recent studies immunology focused on elimination transgene-expressing cells adaptive system, yet innate system also critical role, both initial response to vector prompting...
Elimination of specific surface-exposed single tyrosine (Y) residues substantially improves hepatic gene transfer with adeno-associated virus type 2 (AAV2) vectors. Here, combinations mutations in the seven potentially relevant Y were evaluated for further augmentation transduction efficiency. These mutant capsids packaged viral genomes to similar titers and retained infectivity. A triple-mutant (Y444+500+730F) vector consistently had highest level vivo murine hepatocytes, approximately...
Lignin nanotubes (LNTs) synthesized from the aromatic plant cell wall polymer lignin in a sacrificial alumina membrane template have as useful features their flexibility, ease of functionalization due to availability many functional groups, label-free detection by autofluorescence, and customizable optical properties. In this report we show that physicochemical properties LNTs can be varied over wide range match requirements for specific applications using with different subunit composition,...
Recombinant adeno-associated viruses (rAAV) have been widely used in gene therapy applications for central nervous system diseases. Though rAAV can efficiently target neurons and astrocytes mouse brains, microglia, the immune cells of brain, are refractile to rAAV. To identify AAV capsids with microglia-specific transduction properties, we initially screened most commonly serotypes, AAV1-9 rh10, on primary microglia cultures. While these were not permissive, then tested microglial targeting...
Adeno-associated viral (AAV) vectors are currently being tested in multiple clinical trials for liver-directed gene transfer to treat the bleeding disorders hemophilia A and B metabolic disorders. The optimal capsid transduction of human hepatocytes has been under active investigation, but results across various models inconsistent. We vivo "humanized" mice. Methods quantitate percent AAV transduced murine chimeric livers were optimized using flow cytometry confocal microscopy with image...
ABSTRACT Although adeno-associated virus type 2 (AAV) has gained attention as a potentially useful alternative to the more commonly used retrovirus- and adenovirus-based vectors for human gene therapy, efficient transfer transgene expression by AAV require that following two obstacles be overcome. First, target cell must express receptor coreceptor infection, second, allow viral second-strand DNA synthesis. We now describe third obstacle, impaired intracellular trafficking of nucleus, which...
A 52 kd cellular protein, FK506-binding protein (FKBP52), phosphorylated at tyrosine residues by epidermal growth factor receptor kinase (EGFR-PTK), inhibits adeno-associated virus 2 (AAV2) second-strand DNA synthesis and transgene expression. FKBP52 is dephosphorylated T-cell phosphatase (TC-PTP), TC-PTP over-expression leads to improved viral In these studies, we observed that perturbation of EGFR-PTK signaling a specific inhibitor, Tyrphostin 23 (Tyr23), augmented the transduction...
The target cell specificity of the B19 parvovirus infection was examined by isolating highly enriched hematopoietic progenitor and stem cells from normal human bone marrow. efficiency replication in erythroid approximately 100-fold greater than that unseparated marrow cells. more-primitive identical to or closely related pluripotent cells, on other hand, did not support viral replication. progeny virus produced infectious strongly suppressed erythropoiesis vitro. susceptibility both...
FK506-binding protein 52 (FKBP52) is a tetratricopeptide repeat that associates with steroid receptors in complexes containing heat shock 90. To investigate the role of FKBP52 steroid-regulated physiology, we generated FKBP52-deficient mice. (-/-) females are sterile due to complete failure implantation, process requires estrogen (ER) and progesterone (PR). Because uterus expresses two forms PR, PR-A PR-B, investigated all three as potential targets action. uteri showed normal growth...
Adeno-associated viruses (AAVs) use a variety of cellular receptors/coreceptors to gain entry into cells. A number AAV serotypes are now available, and the cognate for only handful those have been identified thus far. Of 10 commonly used serotypes, AAV3 is by far least efficient in transducing cells general. However, our more recent studies, we observed that vectors transduced human liver cancer remarkably well, which led hypothesis uses hepatocyte growth factor receptor (HGFR) as coreceptor...