A5083918038- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Viral gastroenteritis research and epidemiology
- Metabolism and Genetic Disorders
- Pancreatic function and diabetes
- Xenotransplantation and immune response
- Pluripotent Stem Cells Research
- HIV/AIDS drug development and treatment
- Tissue Engineering and Regenerative Medicine
- Hepatitis C virus research
- Renal Transplantation Outcomes and Treatments
- HIV Research and Treatment
- Patient Satisfaction in Healthcare
- Organ Transplantation Techniques and Outcomes
- Folate and B Vitamins Research
- Liver physiology and pathology
- Animal Genetics and Reproduction
- Healthcare Systems and Technology
- Liver Disease and Transplantation
- Reliability and Agreement in Measurement
- Mitochondrial Function and Pathology
- Anesthesia and Neurotoxicity Research
- Immune Cell Function and Interaction
- Liver Disease Diagnosis and Treatment
- Biochemical and Molecular Research
WinnMed
2021-2023
Mayo Clinic in Arizona
2017-2022
Mayo Clinic
2018-2021
Mayo Clinic in Florida
2020
Importance There was a shift in patient volume from in-person to video telemedicine visits during the COVID-19 pandemic. Objective To determine concordance of provisional diagnoses established at visit with an for patients presenting new clinical problem. Design, Setting, and Participants This is diagnostic study who underwent consultation followed by outpatient same problem specialty within 90-day window. The diagnosis made compared reference standard 2 blinded, independent medical...
Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by deficiency of fumarylacetoacetate hydrolase (FAH). It has been previously shown that ex vivo hepatocyte-directed gene therapy using integrating lentiviral vector to replace the defective Fah can cure liver disease in small- and large-animal models HT1. This study hypothesized editing CRISPR/Cas9 could be used correct a mouse model HT1, which single point mutation results loss FAH function. To achieve high...
Abstract Conventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)−1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression liver fibrosis, failure, activation of tumorigenic pathways. Here we demonstrate cure HT1 by direct, vivo administration a therapeutic lentiviral vector targeting the expression human fumarylacetoacetate hydrolase ( FAH ) transgene porcine model HT1. This is well tolerated provides stable...
Ex vivo CRISPR/Cas9‐mediated gene editing in hepatocytes using homology‐directed repair (HDR) is a potential alternative curative therapy to organ transplantation for metabolic liver disease. However, major limitation of this approach quiescent adult primary that nonhomologous end‐joining the predominant DNA pathway double‐strand breaks (DSBs). This study explored hypothesis ex hepatocyte culture could reprogram favor HDR after DSBs. Quantitative PCR (qPCR), RNA sequencing, and flow...
Orthotopic liver transplantation remains the only curative therapy for inborn errors of metabolism. Given tremendous success primary immunodeficiencies using ex-vivo gene with lentiviral vectors, there is great interest in developing similar therapies metabolic diseases. We have previously generated a pig model hereditary tyrosinemia type 1 (HT1), an autosomal recessive disorder caused by deficiency fumarylacetoacetate hydrolase (FAH). Using this model, we demonstrated and cell vector to...
A cure for HIV would require eliminating cells that contain the virus in a latent form from body. Current antiretroviral medications are unable to rid body of latently infected cells. Here, we show combination investigational agents—ixazomib plus venetoclax—which reactivate and predispose apoptosis may reduce T cell model, but at expense nonspecific toxicity primary
Inborn errors of metabolism (IEMs) often result from single-gene mutations and collectively cause liver dysfunction in neonates leading to chronic systemic disease. Current treatments for many IEMs are limited maintenance therapies that may still require orthotropic transplantation. Gene offer a potentially superior approach by correcting or replacing defective genes with functional isoforms; however, they face unique challenges complexities presented individual diseases their diverse...
The effectiveness of cell-based therapies to treat liver failure is often limited by the diseased environment. Here, we provide preclinical proof concept for hepatocyte transplantation into lymph nodes as a cure in large-animal model with hereditary tyrosinemia type 1 (HT1), metabolic disease caused deficiency fumarylacetoacetate hydrolase (FAH) enzyme. Autologous porcine hepatocytes were transduced
Abstract Phenylketonuria (PKU) is the most common inborn error of metabolism liver, and results from mutations both alleles phenylalanine hydroxylase gene ( PAH ). As such, it a suitable target for therapy via delivery with recombinant adeno‐associated virus (AAV) vector. Here we use synthetic AAV vector Anc80 systemic administration to deliver functional copy codon‐optimized human gene, or without an intron spacer, Pah enu2 mouse model PKU. Dose‐dependent transduction liver expression mRNA...
Gene therapy is an ideal choice to cure many inborn errors of metabolism the liver. Ex-vivo, lentiviral vectors have been used successfully in treatment hematopoietic diseases humans, as their use offers stable transgene expression due vector's ability integrate into host genome. This method demonstrates application ex vivo gene hepatocytes a large animal model hereditary tyrosinemia type I. process consists 1) isolation primary from autologous donor/recipient animal, 2) delivery via...
Phenylketonuria (PKU) is a metabolic disorder whereby phenylalanine metabolism deficient due to allelic variations in the gene for hydroxylase ( PAH ). There no cure PKU other than orthotopic liver transplantation, and standard of care patients limited dietary restrictions key amino acid supplementation. Therefore, Pah was edited pig fibroblasts generation clone piglets that harbor common severe human mutation, R408W. Additionally, proximal region mutation further humanized by introducing 5...
Abstract The effectiveness of cell-based therapies to treat liver failure is limited by the diseased environment. Herein we provide preclinical proof-of-concept for treatment through hepatocyte transplantation into lymph nodes in a large-animal model hereditary tyrosinemia type 1 (HT1), metabolic disease caused deficiency fumarylacetoacetate hydrolase (FAH) enzyme. FAH-deficient pigs received autologous mesenteric after ex vivo transduction with lentiviral vector carrying pig Fah gene....
OBJECTIVES/GOALS: The goal of this study is to examine the incidence, etiology, and outcomes hepatocellular carcinoma (HCC) in a 27-county region SE Minnesota W Wisconsin between 2010 2021. A comparison first second half period will be made look for possible trends. METHODS/STUDY POPULATION: Rochester Epidemiology Project (REP) database patient records across Wisconsin. Starting 2010, REP opened catchment area, which includes over 1.3 million patients with population coverage approximately...
Abstract Conventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression liver fibrosis, failure, activation of tumorigenic pathways. Here we demonstrate the first time a cure HT1 by direct, vivo administration therapeutic lentiviral vector targeting expression human fumarylacetoacetate hydrolase ( FAH ) transgene porcine model HT1. This was well tolerated provided...