A5028322068- Virus-based gene therapy research
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- Neonatal Respiratory Health Research
- Virology and Viral Diseases
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Energy Harvesting in Wireless Networks
- Cystic Fibrosis Research Advances
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Parvovirus B19 Infection Studies
- Renin-Angiotensin System Studies
- Viral Infections and Outbreaks Research
- Viral Infections and Immunology Research
- Tracheal and airway disorders
- CAR-T cell therapy research
- bioluminescence and chemiluminescence research
- Hormonal Regulation and Hypertension
- Cancer Research and Treatments
- Animal Virus Infections Studies
- Viral Infections and Vectors
- Congenital Diaphragmatic Hernia Studies
- Optical Imaging and Spectroscopy Techniques
- Infectious Diseases and Mycology
University of Iowa
2016-2025
Cystic Fibrosis Foundation
2024
Iowa City Public Library
2024
Gene Therapy Laboratory
2002-2019
Pediatrics and Genetics
2011
The glycoproteins (GP) of enveloped viruses facilitate entry into the host cell by interacting with specific cellular receptors. Despite extensive study, a receptor for deadly filoviruses Ebolavirus and Marburgvirus has yet to be identified characterized. Here, we show that T-cell Ig mucin domain 1 (TIM-1) binds binding Zaire Ebola virus (EBOV) glycoprotein, ectopic TIM-1 expression in poorly permissive cells enhances EBOV infection 10- 30-fold. Conversely, reduction cell-surface RNAi...
Significance DNA transposons that translocate by excision from a donor site and insertion into target are often used for genome engineering insertional mutagenesis transgenesis. The piggyBac element is especially useful because it can excise precisely an site, restoring the to its pretransposon state. Precise particularly when transient transgenesis needed, example, in introduction of transcription factors induced pluripotent stem cell production. We have generate Excision + Integration −...
The current model of measles virus (MV) pathogenesis implies that apical infection airway epithelial cells precedes systemic spread. An alternative suggests primarily infected lymphatic carry MV to the basolateral surface cells, supporting shedding into lumen and contagion. This predicts a mutant MV, unable enter through unidentified cell receptor (EpR), would remain virulent but not be shed. To test this model, we identified residues attachment protein sustaining EpR-mediated fusion. These...
Bioluminescence tomography (BLT) is a new molecular imaging mode, which being actively developed to reveal and cellular signatures as labeled by bioluminescent probes in living small animal. This technology can help diagnose diseases, evaluate therapies, facilitate drug development with mouse models. In this paper, we describe vivo experiments BLT, propose the reconstruction procedure of sources from optical data measured on body surface using modality fusion approach. The results show...
Different approaches are used in the production of recombinant adeno-associated virus (rAAV). The two leading transiently transfected human HEK293 cells and live baculovirus infection Spodoptera frugiperda (Sf9) insect cells. Unexplained differences vector performance have been seen clinically preclinically. Thus, we performed a controlled comparative analysis varying only host cell species but maintaining all other parameters. We characterized with multiple analytical approaches: proteomic...
Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in CF transmembrane conductance regulator (CFTR), resulting defective anion transport. Regardless of the disease-causing mutation, gene therapy a strategy to restore transport airway epithelia. Indeed, viral vector–delivered CFTR can complement channel defect. In this proof-of-principle study, functional vivo activity was restored airways pigs using feline immunodeficiency virus–based (FIV-based) lentiviral vector...
The volume and composition of a thin layer liquid covering the airway surface defend lung from inhaled pathogens debris. Airway epithelia secrete Cl- into through cystic fibrosis transmembrane conductance regulator (CFTR) channels, thereby increasing liquid. discovery that pulmonary ionocytes contain high levels CFTR led us to predict drive secretion. However, we found opposite. Elevating ionocyte abundance increased absorption, whereas reducing In contrast other epithelial cells, contained...
ABSTRACT Vectors derived from lentiviruses provide a promising gene delivery system. We examined the in vivo transfer efficiency and tissue or cell tropism of feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with glycoproteins Ross River Virus (RRV). RRV were efficiently incorporated into FIV virions, generating preparations vector, which after concentration attain titers up to 1.5 × 10 8 TU/ml. After systemic administration, RRV-pseudotyped vectors (RRV/FIV)...
The physiological components that contribute to cystic fibrosis (CF) lung disease are steadily being elucidated. Gene therapy could potentially correct these defects. CFTR-null pigs provide a relevant model test gene vectors. Using an in vivo selection strategy amplifies successful capsids by replicating their genomes with helper adenovirus coinfection, we selected adeno-associated virus (AAV) tropism for pig airway epithelia. evolved capsid, termed AAV2H22, is based on AAV2 5 point...
Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve a novel effective prophylactic or treatment option. Using mouse-adapted virus, we found that murine gamma administered 24 hours before after infection robustly protects lethally-challenged mice reduces morbidity serum viral titers. Furthermore, demonstrated profoundly...
Mutations in the CFTR gene that lead to premature stop codons or splicing defects cause cystic fibrosis (CF) and are not amenable treatment by small-molecule modulators. Here, we investigate use of adenine base editor (ABE) ribonucleoproteins (RNPs) convert A•T G•C pairs as a therapeutic strategy for three CF-causing mutations. Using ABE RNPs, corrected human airway epithelial cells codon mutations (R553X W1282X) splice-site mutation (3849 + 10 kb C > T). Following delivery, DNA sequencing...
The practical application of gene therapy as a treatment for cystic fibrosis is limited by poor transfer efficiency with vectors applied to the apical surface airway epithelia. Recently, folate receptor alpha (FR alpha), glycosylphosphatidylinositol-linked protein, was reported be cellular filoviruses. We found that polarized human epithelia expressed abundant FR on their surface. In an attempt target these receptors, we pseudotyped feline immunodeficiency virus (FIV)-based using envelope...
Gene transfer development for treatment or prevention of cystic fibrosis lung disease has been limited by the inability vectors to efficiently and persistently transduce airway epithelia. Influenza A is an enveloped virus with natural tropism; however, pseudotyping feline immunodeficiency (FIV)-based lentiviral vector hemagglutinin envelope protein proved unsuccessful. Conversely, FIV from influenza D (Thogoto GP75) resulted in titers 10(6) transducing units (TU)/ml conferred apical entry...
For many envisioned applications of lentivirus vectors as tools in respiratory biology and therapeutic gene delivery, the efficiency transfer must be improved. We previously demonstrated stable, persistent (>11 months) vivo expression following a single application feline immunodeficiency virus (FIV)-based vector (GP64-FIV) to murine nasal epithelia. Here we investigate efficacy repeated administration airways. Using quantitative bioluminescent imaging, found that consecutive daily dosing...
To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. Candidate were identified by using EBOV GP virions transduce human tumor cell lines that had previously been characterized cDNA microarray. Transduction profiles each these generated, and a significant positive correlation was observed between RhoC permissivity vector This not specific alone as...
ABSTRACT The discovery that measles virus (MV) uses the adherens junction protein nectin-4 as its epithelial receptor provides a new vantage point from which to characterize rapid spread in airway epithelium. We show here well-differentiated primary cultures of cells human donors (HAE), MV infectious centers form rapidly and become larger than those other respiratory pathogens: syncytial virus, parainfluenza 5, Sendai virus. While visible syncytia do not after infection HAE, cytoplasm an...
ABSTRACT Measles virus (MeV) is a highly contagious respiratory transmitted via aerosols. To understand how MeV exits the airways of an infected host, we use unpassaged primary cultures human airway epithelial cells (HAE). typically remains cell-associated in HAE and forms foci infection, termed infectious centers, by directly spreading cell-to-cell. We previously described phenomenon which centers detach en masse from remain viable. Here, investigate mechanism this cellular detachment. Via...
Sinn, Patrick L., and Curt D. Sigmund. Identification of three human renin mRNA isoforms from alternative tissue-specific transcriptional initiation. Physiol Genomics 3: 25–31, 2000.—We have reported that mice transgenic for 140- 160-kb P1 phage artificial chromosomes (PACs) containing the gene express in a highly tissue-restricted regulated manner. Herein, we demonstrate transgene is also expressed appropriately throughout development. In course this investigation, identified existence...