Header Logo

Search Result Details

This page shows the details of why an item matched the keywords from your search.
One or more keywords matched the following properties of Flotte, Terence
PropertyValue
overview

Dr Flotte received his undergraduate degree in the biological sciences from the University of New Orleans in 1982, and his medical degree from the Louisiana State University School of Medicine in 1986. After serving his residency in pediatrics at Johns Hopkins University, he completed a pediatric pulmonary fellowshipa and postdoctoral training in molecular virology there in 1992.

In 1995, Dr. Flotte and his colleagues at Johns Hopkins became the first to use adeno-associated virus, or AAV, as a vehicle to deliver corrective genes to targeted sites in the body, including the damaged airways of adults with cystic fibrosis.

In 1996, Dr Flotte joined the faculty of the University of Florida and was appointed Associate Director of UF’s Powell Gene Therapy Center. In 2000, he was named Director of the Powell Center and founding Director of the newly established UF Genetics Institute, a cross-campus multidisciplinary unit encompassing gene therapy, human genetics, agricultural genetics and comparative genomics. In 2002, Flotte stepped down from these roles to accept the position of Chair of the Department of Pediatrics.

An internationally known pioneer in human gene therapy, Flotte is currently investigating the use of gene therapy for genetic diseases that affect children, including cystic fibrosis, alpha-1 antitrypsin (AAT) deficiency, type I diabetes, and disorders of fatty acid oxidation. He is currently conducting Phase I trials with rAAV expressing alpha-1antitrypsin in AAT-deficient patients. He has also focused on the study of adeno-associated virus (AAV) vectors. Dr. Flotte's laboratory has also focused on the mechanisms of AAV persistence, since these represent the basis for a more profound understanding of the potential for long-term safe and effective gene therapy.

Office of the Dean Website

Research

Recombinant adeno-associated virus (AAV) gene therapy vectors for, cystic fibrosis (CF), alpha-1-antitrypsin deficiency (AAT) and fatty oxidation disorders (FAO)

adeno virusAAV is a non-pathogenic human parvovirus which is commonly isolated from the respiratory tract of humans (Figure 1A). AAV’s life cycle includes a unique mechanism for persistence in human cells by means of site-specific integration into a region of chromosome 19, the AAVS1 site (Figure 1B). In 1993, our group published the results of the first successful in vivo gene transfer with AAV. In that study, AAV vectors carrying the human CF transmembrane conductance regulator (CFTR) gene were delivered to the bronchial epithelium of rabbits. Efficient gene transfer was observed which persisted for over 6 months without any detectable toxicity. Subsequently, we studied AAV-CFTR gene transfer in rhesus macaques. Our studies in rhesus served two purposes: 1.We performed the primary toxicology study to justify beginning our phase I trial of AAV-CFTR administration in humans, and 2. we studied vector integration and persistence in vivo for the first time. Since then our laboratory has gone on to perform phase I clinical trials delivering AAV2 expressing the CFTR gene in CF patients. Much has been learned form the early trials including that paucity of AAV2 receptors on the luminal side of the airways and the weak promoter activity in early vectors. This limited the efficiency and efficacy of the viral vectors used in the early trials. To overcome this, the lab has designed a more robust expression cassette delivering a CFTR ‘mini’ gene and has determined that AAV1 is far superior to AAV2 at transducing airways. These new generation viral vectors for CF gene therapy are currently undergoing pre-clinical testing and will soon be tested in patients. Our laboratory has also pioneered phase I clinical studies using intra-muscular administration of rAAV2 as well as this more novel AAV1 serotype expressing the gene for alpha-1-antitrypsin (AAT) in AAT deficient patients. We are also developing hybrid rAAV-RNAi approaches to treat AAT deficient liver disease in which a toxic gain of function of the mutant protein contributes to the pathology. The laboratory is also involved in gene therapy for fatty oxidation disorders. Specifically we are developing gene delivery for the Acyl-CoA Dehydrogenases family enzymes that initiate the first step of the B-oxidation pathway.

Current Studies in Cystic Fibrosis

CFTR+/+Cystic fibrosis (CF), the most common lethal, single-gene disorder affecting Northern Europeans and North Americans, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR is a chloride channel and a regulator of other ion channels, and many aspects of the CF phenotype are directly related to ion channel abnormalities attributable to CFTR mutation. What remains less clear, however, is how CFTR mutation leads to persistent endobronchial infection with Pseudomonas aeruginosa and severe airway inflammation which are the hallmarks of the lung pathology in CF. One theory, which remains controversial, contends that CFTR mutation primes CF cells to release greater quantities of pro-inflammatory cytokines than non-CF cells. One line of evidence in support of this theory is a Pseudomonas agarose bead airway infection model, in which CFTR knockout mice demonstrate greater weight loss and mortality and higher levels of pro-inflammatory cytokines than control mice. One of the limitations of this model has been its technical complexity and a wide variability of responses among individual animals. Because of the need for a technically simpler mouse model for inflammatory lung disease in CF, our laboratory has recently developed a new approach based on Aspergillus fumigatus (Af) sensitization and challenge. This model reproduces certain key immunologic and pathologic aspects of allergic bronchopulmonary aspergillosis (ABPA) an inflammatory lung phenotype that is much more common in CF patients than in any other clinical context. In the animal model studies, CFTR knockout mice demonstrated up-regulated levels of IL4 prior to sensitization, and subsequent to sensitization developed a hyper-IgE response and markedly divergent cytokine expression (including increased IL13, IL4, IL2, IL10, and KC) as compared with non-CF. While this CFTR-dependent inflammatory phenotype is potentially very promising, it has raised more questions than it answered. In particular, the divergence of expression of cytokines that are predominantly produced within lymphocytes, macrophages and other non-epithelial cells raises the possibility of an important role of CFTR itself in non-epithelial cells. Therefore our lab is currently studying which cell types contribute primarily to the CF-dependent inflammatory lung disease phenotype in Aspergillus-sensitized CF mice? What pathways or other mechanisms might be aberrantly regulated in affected cells?

Gene and RNAi Therapy for Alpha-1 Antitrypsin

Protease - Induced Lung DamageAlpha-1 antitrypsin (AAT) is one of the primary circulating serum antiproteases in humans. It inhibits a variety of serine proteinases, with neutrophil elastase being one of the most physiologically important, as well as inhibiting a number of metallo-proteinases and other pro-inflammatory and pro-apoptotic molecules. AAT is normally produced within hepatocytes and macrophages, where hepatocyte-derived AAT forms the bulk of the physiologic reserve of AAT. Approximately 4% of the North American and Northern European populations possess at least one copy of a mutant allele, known as PI*Z, which results from a single amino acid substitution of Lys for Glu at position 342. In the homozygous state, this mutation leads to severe deficiency of AAT, and can result in two distinct pathologic states: a lung disease which is primarily due to the loss of antiprotease function, and a liver disease (present to a significant degree in only 10% of patients) which is due to a toxic gain of function of the Z-AAT mutant protein. The mutation of Z-AAT leads to the loss of a crucial salt-bridge in a beta sheet region of the protein, allowing for the insertion of the reactive loop of a neighboring AAT molecule in between the two beta sheets. The structure of the resultant very stable loop-sheet polymers has been solved and provides insight into how the mutant may accumulate in a misfolded configuration. This accumulation within hepatocytes consistently results in a state of serum deficiency due to inefficient secretion. In individuals affected by AAT liver disease, it also triggers a cascade of aberrant signals within the hepatocyte, most likely the result of an unfolded protein response. However, the downstream details remain unclear, as does the reason for the disparity between those Z-homozygotes who develop liver disease and those who do not. Regardless of the precise mechanism by which Z-AAT conformational changes lead to liver disease, there is general consensus that molecular therapies for AAT liver disease should act by down-regulating Z-AAT. Our group has developed two different investigational clinical gene therapy products for gene augmentation of AAT as a potential therapy for the lung disease (rAAV2-AAT and rAAV1-AAT) (1, 4), and we have a third vector in development that is much more efficient for delivery of wild-type (M) AAT to hepatocytes (rAAV8-AAT). Given the need for down-regulation of Z-AAT, we have also begun to examine a number of innovative approaches to long-term expression of therapeutic RNAs using the recombinant adeno-associated virus (rAAV) platform, including spliceosome-mediated RNA trans-splicing (SMaRT), and rAAV-mediated in vivo delivery of RNAi in Z-AAT transgenic mice, a project which was recently published from our laboratory. The constructs in that paper utilized a pol III promoter (U6) to express short hairpin RNAs (shRNAs) targeting three different sites on the AAT molecule, but were not specific to the mutant allele. While it is feasible to direct silencing agents to the liver to decrease Z-AAT expression, while directing gene augmentation to other sites, the hepatocyte is most likely the optimal target for augmentation as well. Our lab is currently focusing on systematically developing RNAi-based approaches to Z-AAT down-regulation within hepatocytes and to devise appropriate strategies that might allow this to be combined with M-AAT gene augmentation

Gene Therapy for Fatty Oxidation Disorders

Genetic disorders of mitochondrial fatty acid oxidation (FAO) represent a relatively common class of metabolic disorders, exceeding more than 1 in 15,000 newborns. These disorders are associated with genes involved in the mitochondrial b-oxidation of fatty acids, which provide fuel once glycogen stores are depleted during prolonged fasting or during times of increased energy demands and physiological stress. During these circumstances liberation from triglycleride stores in adipose tissue causes free fatty acids circulate to the liver and striated muscle. After the fatty acids diffuse (short chain) or are actively transported (long chain) across the cellular and mitochondrial membranes, the oxidation of fatty acids occurs within the mitochondrial matrix. b-oxidation proceeds in a cyclical fashion resulting in the removal of sequential 2-carbon units as acetyl-CoA, for entry into the TCA cycle

Importantly, the first step of each cycle in the mitochondrial matrix is catalyzed by an acyl-CoA dehydrogenase. This rate limiting function is performed by a family of enzymes that differ in their substrate specificity based on the carbon chain length of the acyl CoA molecule. The acyl-CoA dehydrogenases (ACDs) are a family of 5 mitochondrial enzymes involved in fatty acid and amino acid metabolism that catalyze the transfer of electrons from various acyl-CoA esters to electron transfer flavoprotein. Very long, medium and short chain acyl-CoA dehydrogenases (VLCAD, MCAD and SCAD) catalyze the first step in the b-oxidation cycle with substrate specificities of 16-, 8- and 4- carbon chains, respectively.

cytosolCurrently our lab is applying rAAV-based transduction of skeletal muscle for those FAO deficiencies that are most common in humans, medium chain acyl CoA dehydrogenase (MCAD) and very long chain acyl CoA dehydrodgenase (VLCAD). Over the past 5 years, mouse models have become available for each of these disorders, and mass newborn screening for FAO disorders has been initiated in many states. Our prior work has relied heavily on rAAV1 pseudotyped vectors for skeletal muscle transduction. The emergence of rAAV9-based vectors now provides the potential for even greater efficiency in using transduction of skeletal muscle and cardiac muscle as a platform for gene therapy of systemic genetic diseases. We are investigating to compare rAAV1 and rAAV9 in the context of a translational application to VLCAD and MCAD deficiencies. Specifically, the feasibility of molecular and biochemical correction of VLCAD and MCAD deficiencies is tested in mouse models of these deficiencies. Our primary focus is on determining whether rAAV9 (vs. rAAV1)-mediated transduction of skeletal and cardiac muscle will result in greater improvement of acyl carnitine profiles (i.e., clearance of abnormally high levels of fatty acyl carnitine metabolites that are characteristic of this disorder) and MRS profiles. We are also going to develop formal preclinical toxicology studies of muscle delivery of rAAV9 or rAAV1-VLCAD and rAAV9 or rAAV1-MCAD which will be completed in anticipation of new phase I clinical trials of gene therapy for these FAO disorders.

One or more keywords matched the following items that are connected to Flotte, Terence
Item TypeName
Academic Article Gene expression from adeno-associated virus vectors in airway epithelial cells.
Academic Article In vivo model of adeno-associated virus vector persistence and rescue.
Academic Article In vivo gene therapy with adeno-associated virus vectors for cystic fibrosis.
Academic Article A phase I/II study of tgAAV-CF for the treatment of chronic sinusitis in patients with cystic fibrosis.
Academic Article Adeno-associated virus vectors for gene therapy of cystic fibrosis.
Academic Article A phase I study of an adeno-associated virus-CFTR gene vector in adult CF patients with mild lung disease.
Academic Article Development of adeno-associated virus vectors for gene therapy of cystic fibrosis.
Academic Article Safety of single-dose administration of an adeno-associated virus (AAV)-CFTR vector in the primate lung.
Academic Article Use of the NADH-quinone oxidoreductase (NDI1) gene of Saccharomyces cerevisiae as a possible cure for complex I defects in human cells.
Academic Article CMV-beta-actin promoter directs higher expression from an adeno-associated viral vector in the liver than the cytomegalovirus or elongation factor 1 alpha promoter and results in therapeutic levels of human factor X in mice.
Academic Article Genetic therapy. Past, present, and future.
Academic Article Gene therapy in cystic fibrosis.
Academic Article Recombinant adeno-associated virus vectors for cystic fibrosis gene therapy.
Academic Article CFTR gene transduction in neonatal rabbits using an adeno-associated virus (AAV) vector.
Academic Article Adeno-associated viral vectors for CF gene therapy.
Academic Article Virus-based gene delivery systems.
Academic Article Intramuscular administration of recombinant adeno-associated virus 2 alpha-1 antitrypsin (rAAV-SERPINA1) vectors in a nonhuman primate model: safety and immunologic aspects.
Academic Article Adeno-associated virus-mediated IL-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of NOD mice.
Academic Article Gene delivery in renal tubular epithelial cells using recombinant adeno-associated viral vectors.
Academic Article The pyruvate dehydrogenase complex as a target for gene therapy.
Academic Article Immunity to adeno-associated virus serotype 2 delivered transgenes imparted by genetic predisposition to autoimmunity.
Academic Article Phase I trial of intramuscular injection of a recombinant adeno-associated virus alpha 1-antitrypsin (rAAV2-CB-hAAT) gene vector to AAT-deficient adults.
Academic Article Gene therapy progress and prospects: recombinant adeno-associated virus (rAAV) vectors.
Academic Article Functional characterization of a recombinant adeno-associated virus 5-pseudotyped cystic fibrosis transmembrane conductance regulator vector.
Academic Article Ex vivo transduced liver progenitor cells as a platform for gene therapy in mice.
Academic Article Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10.
Academic Article Adeno-associated virus-mediated gene transfer for lung diseases.
Academic Article Correlation between DNA transfer and cystic fibrosis airway epithelial cell correction after recombinant adeno-associated virus serotype 2 gene therapy.
Academic Article Efficient hepatic delivery and expression from a recombinant adeno-associated virus 8 pseudotyped alpha1-antitrypsin vector.
Academic Article Therapeutic level of functional human alpha 1 antitrypsin (hAAT) secreted from murine muscle transduced by adeno-associated virus (rAAV1) vector.
Academic Article Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injection.
Academic Article Safety and biological efficacy of an adeno-associated virus vector-cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus.
Academic Article Recombinant adeno-associated virus vector-based gene transfer for defects in oxidative metabolism.
Academic Article IL-10 regulation of lupus in the NZM2410 murine model.
Academic Article Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain.
Academic Article Inhibition of recombinant adeno-associated virus (rAAV) transduction by bronchial secretions from cystic fibrosis patients.
Academic Article Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults.
Academic Article Preclinical characterization of a recombinant adeno-associated virus type 1-pseudotyped vector demonstrates dose-dependent injection site inflammation and dissemination of vector genomes to distant sites.
Academic Article Progress and prospects: gene therapy clinical trials (part 1).
Academic Article Partial correction of the CFTR-dependent ABPA mouse model with recombinant adeno-associated virus gene transfer of truncated CFTR gene.
Academic Article Recombinant adeno-associated virus-mediated global anterograde delivery of glial cell line-derived neurotrophic factor to the spinal cord: comparison of rubrospinal and corticospinal tracts in the rat.
Academic Article In utero efficacy of cystic fibrosis gene therapy: difficult studies, positive or negative.
Academic Article Towards a rAAV-based gene therapy for ADA-SCID: from ADA deficiency to current and future treatment strategies.
Academic Article Gene therapy for cystic fibrosis.
Academic Article Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.
Academic Article In vitro and in vivo functional characterization of gutless recombinant SV40-derived CFTR vectors.
Academic Article Gene therapy for cystic fibrosis.
Academic Article Recombinant adeno-associated virus gene therapy for cystic fibrosis and alpha(1)-antitrypsin deficiency.
Academic Article Adeno-associated virus (AAV) as a vehicle for therapeutic gene delivery: improvements in vector design and viral production enhance potential to prolong graft survival in pancreatic islet cell transplantation for the reversal of type 1 diabetes.
Academic Article Preclinical evaluation of a recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin made using a recombinant herpes simplex virus production method.
Academic Article Recombinant adeno-associated virus-mediated gene transfer for the potential therapy of adenosine deaminase-deficient severe combined immune deficiency.
Academic Article Gene therapy for alpha-1 antitrypsin deficiency.
Academic Article Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing a1-antitrypsin: interim results.
Academic Article The role of gene and cell therapy in the era of health care reform.
Academic Article Preclinical study design for rAAV.
Academic Article Improved method of recombinant AAV2 delivery for systemic targeted gene therapy.
Academic Article A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies.
Academic Article Gene therapy for pyruvate dehydrogenase E1alpha deficiency using recombinant adeno-associated virus 2 (rAAV2) vectors.
Academic Article Recombinant adeno-associated virus integration sites in murine liver after ornithine transcarbamylase gene correction.
Academic Article Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression.
Academic Article Targeting recombinant adeno-associated virus vectors to enhance gene transfer to pancreatic islets and liver.
Academic Article Systemic overexpression of IL-10 induces CD4+CD25+ cell populations in vivo and ameliorates type 1 diabetes in nonobese diabetic mice in a dose-dependent fashion.
Academic Article Successful transgene expression with serial doses of aerosolized rAAV2 vectors in rhesus macaques.
Academic Article Recombinant adeno-associated virus-mediated alpha-1 antitrypsin gene therapy prevents type I diabetes in NOD mice.
Academic Article Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector.
Academic Article Prospects for virus-based gene therapy for cystic fibrosis.
Academic Article Immune responses to recombinant adeno-associated virus vectors: putting preclinical findings into perspective.
Academic Article Recombinant adeno-associated virus vectors for gene therapy.
Academic Article Functional expression of the single subunit NADH dehydrogenase in mitochondria in vivo: a potential therapy for complex I deficiencies.
Academic Article Recent developments in recombinant AAV-mediated gene therapy for lung diseases.
Academic Article Localized gene expression following administration of adeno-associated viral vectors via pancreatic ducts.
Academic Article Adeno-associated virus-based gene therapy for inherited disorders.
Academic Article Systemic correction of a fatty acid oxidation defect by intramuscular injection of a recombinant adeno-associated virus vector.
Academic Article Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis.
Academic Article Viral vector-mediated and cell-based therapies for treatment of cystic fibrosis.
Academic Article Expression of a truncated cystic fibrosis transmembrane conductance regulator with an AAV5-pseudotyped vector in primates.
Academic Article Gene therapy: the first two decades and the current state-of-the-art.
Academic Article In vivo post-transcriptional gene silencing of alpha-1 antitrypsin by adeno-associated virus vectors expressing siRNA.
Academic Article The promise of gene therapy for the treatment of alpha-1 antitrypsin deficiency.
Academic Article Clinical gene therapy using recombinant adeno-associated virus vectors.
Academic Article Biochemical correction of short-chain acyl-coenzyme A dehydrogenase deficiency after portal vein injection of rAAV8-SCAD.
Academic Article Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics.
Academic Article The pros and cons of immunomodulatory IL-10 gene therapy with recombinant AAV in a Cftr-/- -dependent allergy mouse model.
Academic Article Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy.
Academic Article Modulation of exaggerated-IgE allergic responses by gene transfer-mediated antagonism of IL-13 and IL-17e.
Academic Article IL-10 delivery by AAV5 vector attenuates inflammation in mice with Pseudomonas pneumonia.
Academic Article N-glycosylation augmentation of the cystic fibrosis epithelium improves Pseudomonas aeruginosa clearance.
Academic Article Autoimmunity in a genetic disease?a cautionary tale.
Academic Article Long-term correction of very long-chain acyl-coA dehydrogenase deficiency in mice using AAV9 gene therapy.
Academic Article Cell and gene therapy for genetic diseases: inherited disorders affecting the lung and those mimicking sudden infant death syndrome.
Academic Article Translating the genomics revolution: the need for an international gene therapy consortium for monogenic diseases.
Academic Article Gene-based therapy for alpha-1 antitrypsin deficiency.
Academic Article Adeno-associated virus vectors for gene therapy.
Academic Article An improved system for packaging recombinant adeno-associated virus vectors capable of in vivo transduction.
Academic Article Gene therapy vectors as drug delivery systems.
Concept Genetic Therapy
Academic Article A single intravenous rAAV injection as late as P20 achieves efficacious and sustained CNS Gene therapy in Canavan mice.
Academic Article Birth of a new therapeutic platform: 47 years of adeno-associated virus biology from virus discovery to licensed gene therapy.
Academic Article What is suppression of anti-adeno-associated virus capsid T-cells achieving?
Academic Article Current status of gene therapy for a-1 antitrypsin deficiency.
Academic Article Stability and compatibility of recombinant adeno-associated virus under conditions commonly encountered in human gene therapy trials.
Academic Article Therapeutic Germ Line Alteration: Has CRISPR/Cas9 Technology Forced the Question?
Academic Article Progress with Recombinant Adeno-Associated Virus Vectors for Gene Therapy of Alpha-1 Antitrypsin Deficiency.
Academic Article The End of the Beginning of Gene Therapy.
Academic Article Ethical Implications of the Cost of Molecularly Targeted Therapies.
Academic Article Delivery of Adeno-Associated Virus Gene Therapy by Intravascular Limb Infusion Methods.
Academic Article Efficient and Targeted Transduction of Nonhuman Primate Liver With Systemically Delivered Optimized AAV3B Vectors.
Academic Article The Role of Patient Advocacy Organizations in Advancing Human Gene Therapy.
Academic Article Recombinant Adeno-Associated Virus Vector Genomes Take the Form of Long-Lived, Transcriptionally Competent Episomes in Human Muscle.
Academic Article Development of rAAV2-CFTR: History of the First rAAV Vector Product to be Used in Humans.
Academic Article A Gene Therapy Scientist's Life Well-Lived.
Academic Article Why Human Gene Therapy Scientists Should Care About Model Organisms.
Academic Article Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy.
Academic Article The Target's the Thing.
Academic Article Gene Drives: Biological Shield or Ecological Menace?
Academic Article Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for a-1-antitrypsin deficiency.
Academic Article The Negative Effects of Immigration Restrictions on the Gene Therapy Community.
Academic Article Gene Therapy 2017: Progress and Future Directions.
Academic Article 5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency.
Academic Article AAV Is Now a Medicine: We Had Better Get This Right.
Academic Article In Vivo Genome Editing Partially Restores Alpha1-Antitrypsin in a Murine Model of AAT Deficiency.
Academic Article Therapeutic Advances in Germany and Beyond.
Academic Article Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy.
Academic Article Airway Basal Cells Are the Key for Cystic Fibrosis Gene Therapy.
Academic Article Severe Toxicity in Nonhuman Primates and Piglets with Systemic High-Dose Administration of Adeno-Associated Virus Serotype 9-Like Vectors: Putting Patients First.
Academic Article Recombinant Adeno-Associated Virus-Based Gene Therapy for Disorders Detected by Newborn Screening: Inherent Limitations of This Approach.
Academic Article The Gene Therapy Resource Program: A Decade of Dedication to Translational Research by the National Heart, Lung, and Blood Institute.
Academic Article Gene and Cell Therapy in China: Highlighting Excellence in the 21st Century : 21.
Academic Article The Renaissance of Gene and Cell Therapy: Florence 2016.
Academic Article Gene Therapy for Alcoholism and Other Substance Use Disorders.
Academic Article Therapeutics: Gene Therapy for Alpha-1 Antitrypsin Deficiency.
Academic Article Survival Advantage of Both Human Hepatocyte Xenografts and Genome-Edited Hepatocytes for Treatment of a-1 Antitrypsin Deficiency.
Academic Article European Society of Gene and Cell Therapy (ESGCT) at 25: A Gene Therapy Community at Its Prime and on the Move.
Academic Article Adeno-Associated Virus-Human Bocavirus 1 Chimeric Vectors: Ferreting Out Their Role in Airway Gene Therapy.
Academic Article Top Five Gene Therapy Stories of 2019.
Academic Article The Year in Review: The Top Five Papers of 2018.
Academic Article What the Gene Therapy Community Should Do About Sexual Harassment.
Academic Article New Horizons for Immune Gene Therapy.
Academic Article AAV9 gene replacement therapy for respiratory insufficiency in very-long chain acyl-CoA dehydrogenase deficiency.
Academic Article Recombinant Adeno-Associated Virus Gene Therapy in Light of Luxturna (and Zolgensma and Glybera): Where Are We, and How Did We Get Here?
Academic Article The rapidly evolving state of gene therapy.
Academic Article Senior Gene Therapy Scientists Take a Stand Against Human Embryo Gene Editing.
Academic Article Epigenome Editing Strategies for Low Back Pain.
Academic Article A Safe and Reliable Technique for CNS Delivery of AAV Vectors in the Cisterna Magna.
Academic Article Prime Editing: A Novel Cas9-Reverse Transcriptase Fusion May Revolutionize Genome Editing.
Academic Article Gene Therapy Untangles the Problem of Chronic Traumatic Encephalopathy.
Academic Article 2020: Gene Therapy Enters Its Fourth Decade.
Academic Article Impact on Women's Health: Gene Therapy in Gynecologic Oncology.
Academic Article Revisiting the "New" Inflammatory Toxicities of Adeno-Associated Virus Vectors.
Academic Article Volume and Infusion Rate Dynamics of Intraparenchymal Central Nervous System Infusion in a Large Animal Model.
Academic Article Moving Forward After Two Deaths in a Gene Therapy Trial of Myotubular Myopathy.
Academic Article Black Lives Matter to Gene Therapy.
Academic Article Writing the Story of Gene Editing and CRISPR: An Interview with Kevin Davies, PhD.
Academic Article Large-scale molecular epidemiological analysis of AAV in a cancer patient population.
Academic Article Women Lead Gene Therapy Science in 2021.
Academic Article Gene Therapy in Global Health: Meeting the Needs of Chinese Patients with Beta-Thalassemia.
Academic Article Immune Responses to Recombinant Adenoviruses As Gene Therapy Vectors and COVID-19 Vaccines: A Two-Edged Sword.
Academic Article In?vivo gene editing works in humans: Results of a phase 1 clinical trial for TTR amyloidosis.
Academic Article AAV gene therapy for Tay-Sachs disease.
Academic Article Gene Therapy for Rare Neurological Disorders.
Academic Article Gene Therapy and the Use of Animal Models: Why Mice Alone Are Not Sufficient.
Academic Article Liver-directed SERPINA1 gene therapy attenuates progression of spontaneous and tobacco smoke-induced emphysema in a1-antitrypsin null mice.
Academic Article Secretion of functional a1-antitrypsin is cell type dependent: Implications for intramuscular delivery for gene therapy.
Academic Article Gene Therapy for Endocrine Disorders: A Promising Intervention.
Academic Article ESGCT 2022: The New Normal for the Gene Therapy Community.
Academic Article Future Directions and Resource Needs for National Heart, Lung, and Blood Institute (NHLBI) Gene Therapy Research: A Report of an NHLBI Workshop.
Academic Article Gene therapy for alpha-1 antitrypsin deficiency: an update.
Academic Article Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.
Academic Article Analyzing clinical observations to better understand and manage immune responses to AAV gene therapies.
Academic Article Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne's Muscular Dystrophy.
Academic Article Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne's Muscular Dystrophy. Reply.
Academic Article Lived Experience with Gene Therapy.
Academic Article Approaches to Therapeutic Gene Editing in Alpha-1 Antitrypsin Deficiency.
Academic Article Delivery of Adeno-Associated Virus Vectors to the Central Nervous System for Correction of Single Gene Disorders.
Search Criteria
  • Gene therapy