A5043254233- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Viral gastroenteritis research and epidemiology
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- Hepatitis B Virus Studies
- HIV/AIDS drug development and treatment
- Animal Virus Infections Studies
- Neuroblastoma Research and Treatments
- Animal Genetics and Reproduction
- Viral Infections and Immunology Research
- Pituitary Gland Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Parvovirus B19 Infection Studies
- Advanced biosensing and bioanalysis techniques
- Virology and Viral Diseases
- Neurogenesis and neuroplasticity mechanisms
- Fecal contamination and water quality
- Redox biology and oxidative stress
- Plant Virus Research Studies
- Single-cell and spatial transcriptomics
Fred Hutch Cancer Center
2015-2024
University of Notre Dame
2020
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2012-2018
Cancer Research Center
2016-2018
North Seattle College
2018
Infectious Disease Research Institute
2016
University of California, Berkeley
2010-2012
Quantitative BioSciences
2010
University of Washington Medical Center
2003-2008
Medical Genetics Center
2005-2008
Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection several species. However, results nonprimates may not predictive of transduction the human retina, because differences eye size and specialized morphology high-acuity fovea. This was a study retina macaque, primate with ocular characteristics most similar that humans.In vivo imaging histology were used examine GFP expression macaque AAV vectors containing...
Intravenous (i.v.) delivery of recombinant adenovirus serotype 5 (Ad5) vectors for gene therapy is hindered by safety and efficacy problems. We have discovered a new pathway involved in unspecific Ad5 sequestration degradation. After i.v. administration, rapidly binds to circulating platelets, which causes their activation/aggregation subsequent entrapment liver sinusoids. Virus-platelet aggregates are taken up Kupffer cells degraded. Ad organs can be reduced platelet depletion prior vector...
Despite an existing effective vaccine, hepatitis B virus (HBV) remains a major public health concern. There are suppressive therapies for HBV, but they remain expensive and inaccessible to many, not all patients respond well. Furthermore, HBV can persist as genomic covalently closed circular DNA (cccDNA) that in hepatocytes even during otherwise therapy facilitates rebound after treatment has stopped. Therefore, the need targets active persistent infections remains. As novel approach treat...
Chronic hepatitis B virus (HBV) infection is a major public health problem. New treatment approaches are needed because current treatments do not target covalently closed circular DNA (cccDNA), the template for HBV replication, and rarely clear virus. We harnessed adeno-associated (AAV) vectors CRISPR-Staphylococcus aureus (Sa)Cas9 to edit genome in liver-humanized FRG mice chronically infected with receiving entecavir. Gene editing was detected livers of five eight HBV-specific...
Wastewater treatment plants are typically monitored using fecal indicator bacteria to ensure adequate microbial water quality of the treated effluent. Fecal exhibit poor correlation with virus fate in environment, including during wastewater treatment. Viral-based source tracking methods have potential overcome this limitation. The recently discovered human gut bacteriophage crAssphage is a promising viral indicator. In current study, primary influent, effluent, secondary and final effluent...
Abstract Anti-HSV therapies are only suppressive because they do not eliminate latent HSV present in ganglionic neurons, the source of recurrent disease. We have developed a potentially curative approach against infection, based on gene editing using HSV-specific meganucleases delivered by adeno-associated virus (AAV) vectors. Gene performed with two anti-HSV-1 combination AAV9, AAV-Dj/8, and AAV-Rh10 can 90% or more DNA mouse models orofacial up to 97% genital infection. Using...
CD46 is used by human group B adenoviruses (Ads) as a high-affinity attachment receptor. Here we show evidence that several Ads utilize an additional receptor for infection of cells, which different from CD46. We tentatively named this X. Competition studies with unlabeled and labeled Ads, recombinant Ad fiber knobs, soluble antibodies revealed three subgroups in terms their usage. Group I (Ad16, -21, -35, -50) nearly exclusively uses II (Ad3, -7p, -14) utilizes X not III (Ad11p) both the...
Abstract We evaluate gene editing of HSV in a well-established mouse model, using adeno-associated virus (AAV)-delivered meganucleases, as potentially curative approach to treat latent infection. Here we show that AAV-delivered but not CRISPR/Cas9, mediate highly efficient HSV, eliminating over 90% from superior cervical ganglia. Single-cell RNA sequencing demonstrates both and individual AAV serotypes are non-randomly distributed among neuronal subsets ganglia, implying improved delivery...
Adenovirus vectors based on human serotype 5 (Ad5) have successfully been used as gene transfer in many therapy-based approaches to treat disease. Despite their widespread application, potential therapeutic applications are limited by the prevalence of vector-neutralizing antibodies within population and inability Ad5-based transduce important target cell types. In an attempt circumvent these problems, we developed Ad 11 (Ad11), since neutralizing Ad11 humans is low. E1-deleted vector...
ABSTRACT Species B human adenoviruses (Ads) are often associated with fatal illnesses in immunocompromised individuals. Recently, species Ads, most of which use the ubiquitously expressed complement regulatory protein CD46 as a primary attachment receptor, have gained interest for gene therapy vectors. In this study, we focused on Ad serotype 35 (Ad35), whose trimeric fiber knob domain binds to three molecules K D (equilibrium dissociation constant) 15.5 nM. To study Ad35 knob-CD46...
Therapeutic in vivo gene editing with highly specific nucleases has the potential to revolutionize treatment for a wide range of human diseases, including genetic disorders and latent viral infections like herpes simplex virus (HSV). However, challenges regarding specificity, efficiency, delivery, safety must be addressed before its clinical application. A key concern is risk off-target effects, which can cause unintended potentially harmful changes. We previously developed curative approach...
Gene transfer vectors containing adenovirus (Ad) serotype 35 (Ad35) fibers have shown promise for cancer and stem cell gene therapy. In this study, we attempted to improve the in vitro vivo infection properties of these by increasing their affinity Ad35 fiber receptor CD46. We constructed Ad either wild-type knob (Ad5/35) or mutants with 4-fold- 60-fold-higher CD46 (Ad5/35+ Ad5/35++, respectively). studies lines, higher affinities Ad5/35+ Ad5/35++ did not translate into correspondingly...
Following acute infection, herpes simplex virus (HSV) establishes latency in sensory neurons, from which it can reactivate and cause recurrent disease. Available antiviral therapies do not affect latent viral genomes; therefore, they prevent reactivation following therapy cessation. One possible curative approach involves the introduction of DNA double strand breaks HSV genomes by rare-cutting endonucleases, leading to mutagenesis essential genes. We tested this an vitro model using...
Fecal indicator bacteria (FIB) are typically used to monitor microbial water quality but poor representatives of viruses due different environmental fate. Viral fecal indicators have been proposed as alternatives FIB; however, data evaluating the persistence emerging viral under realistic conditions is necessary evaluate their potential application. In this study, we examined five indicators, including crAssphage and pepper mild mottle virus (PMMoV), three bacterial (E. coli, enterococci...
Recent attempts to circumvent the limitations of adenovirus (Ad) vectors derived from species C serotype Ad5 have focused on use alternative human serotypes. These new serotypes multiple benefits including a low prevalence neutralizing antibodies in humans and alternate tropisms. To investigate characteristics alternatives vectors, we compared biodistribution safety Ads B (Ad3, 11p, 35), (Ad5), E (Ad4), F (Ad41), or chimeric viruses containing Ad11 Ad35 fibers (Ad5/11 Ad5/35), after...
Most chronic viral infections are managed with small molecule therapies that inhibit replication but not curative because non-replicating forms can persist despite decades of suppressive treatment. There therefore numerous strategies in development to eradicate all viruses from the body. We currently engineering DNA cleavage enzymes specifically target hepatitis B virus covalently closed circular (HBV cccDNA), episomal form persists potent antiviral therapies. enzymes, including homing...