4,237 results match your criteria Human Gene Therapy [Journal]


Safe and sustained expression of human iduronidase after adeno-associated virus 9 intrathecal administration in infant rhesus monkeys.

Hum Gene Ther 2019 Apr 24. Epub 2019 Apr 24.

University of Pennsylvania, Gene Therapy Program , Suite 2000 TRL , 125 S. 31st Street , Philadelphia, Pennsylvania, United States , 19104.

Many neuropathic diseases cause early, irreversible neurologic deterioration, which warrants therapeutic intervention during the first months of life. In the case of mucopolysaccharidosis type I (MPS I), a recessive lysosomal storage disorder that results from a deficiency of the lysosomal enzyme, α-l-iduronidase (IDUA), one of the most promising treatment approaches is to restore enzyme expression through gene therapy. Specifically, administering neurotropic adeno-associated virus (AAV) encoding IDUA into the cerebrospinal fluid (CSF) via suboccipital administration has demonstrated remarkable efficacy in large animals. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2019.012DOI Listing

miR-632 functions as oncogene in hepatocellular carcinoma via targeting MYCT1.

Hum Gene Ther Clin Dev 2019 Apr 15. Epub 2019 Apr 15.

Affiliated Hospital of Youjiang Medical University for Nationalities, Department of Pathology , Baise, Guangxi 533000, P. R. China , Baise, China , 533000 ;

microRNAs (miRNAs) have been widely recognized as crucial regulators for tumorigenesis. However, the role of miR-632 in hepatocellular carcinoma (HCC) remains largely unknown. miR-632 expression in HCC cell lines was determined by quantitative real-time PCR. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/humc.2019.040
Publisher Site
http://dx.doi.org/10.1089/humc.2019.040DOI Listing
April 2019
1 Read

Constraints on human CD34+ cell fate due to lentiviral vectors can be relieved by valproic acid.

Hum Gene Ther 2019 Apr 12. Epub 2019 Apr 12.

Ecole Pratique des Hautes Etudes, PSL Research University, UMRS_951, Genethon,, Evry, France ;

The initial stages following the in vitro cytokine stimulation of human cord blood CD34+ cells overlap with the period when lentiviral gene transfer is typically performed. We used single-cell transcriptional profiling and time-lapse microscopy to investigate how the vector-cell crosstalk impacts on the fate decision process. We analyzed the single-cell transcription profiles using a new algorithm and show that lentiviral transduction during the early stages of stimulation modifies the dynamics of the fate choice process of the CD34+ cells. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/hum.2019.009
Publisher Site
http://dx.doi.org/10.1089/hum.2019.009DOI Listing
April 2019
1 Read

The Landscape of Cellular and Gene Therapy Products: Cost, Approvals, and Discontinuations.

Hum Gene Ther Clin Dev 2019 Apr 10. Epub 2019 Apr 10.

University of California San Francisco, 8785, School of Pharmacy, San Francisco, California, United States ;

Background The past 10 years witnessed a significant increase in the approval of cellular and gene therapy products worldwide. The US Food and Drug Administration (FDA) approved 3 gene therapy products within the last 4 months of 2017. The objective of this study was to examine the approval characteristics, discontinuations and cost of all cellular and gene therapy products approved worldwide. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/humc.2018.201
Publisher Site
http://dx.doi.org/10.1089/humc.2018.201DOI Listing
April 2019
12 Reads

LncRNA HOXA-AS3 sponges miR-29c to facilitate cell proliferation, metastasis and EMT process, and activate the MEK/ERK signaling pathway in hepatocellular carcinoma.

Hum Gene Ther Clin Dev 2019 Apr 9. Epub 2019 Apr 9.

Hangzhou, China ;

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with high morbidity and mortality across the world. Recent findings have suggested that lncRNA HOXA-AS3 plays an important role in tumorigenesis and metastasis in a variety of cancers. However, the role of lncRNA HOXA-AS3 in the initiation and progression of HCC remains largely unclear. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2018.266DOI Listing

New Horizons for Immune Gene Therapy.

Hum Gene Ther 2019 Apr;30(4):379-380

2 Editor-in-Chief.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2019.29085.abaDOI Listing

MALAT1-driven inhibition of Wnt signal impedes proliferation and inflammation in fibroblast-like synoviocytes through CTNNB1 promoter methylation in rheumatoid arthritis.

Hum Gene Ther 2019 Mar 26. Epub 2019 Mar 26.

Department of Rheumatology, Affiliated Changzhou Second Hospital of Nanjing Medical University, No. 29, Xing Long Lane, Tianning District, Changzhou 213000, Jiangsu Province, P. R. ChinaChangzhou , China , 213000 ;

Fibroblast-like synoviocytes (FLSs) participate in the pathogenesis of rheumatoid arthritis (RA). Emerging evidence has highlighted the role of long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and its potential involvement in RA. In this study, we test the hypothesis that the MALAT1 might inhibit proliferation and inflammatory response of FLSs in RA. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.212DOI Listing
March 2019
1 Read

The Alpha-1-Antitrypsin Promoter Improves the Efficacy of an AAV Vector for the Treatment of MNGIE.

Hum Gene Ther 2019 Apr 24. Epub 2019 Apr 24.

1 Research Group on Neuromuscular and Mitochondrial Diseases, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; Paris, France.

MNGIE (mitochondrial neurogastrointestinal encephalomyopathy) is a devastating disease caused by mutations in , which encodes thymidine phosphorylase (TP). In MNGIE patients, TP dysfunction results in systemic thymidine and deoxyuridine overload, which interferes with mitochondrial DNA replication. Preclinical studies have shown that gene therapy using a lentiviral vector targeted to hematopoietic stem cells or an adeno-associated vector (AAV) transcriptionally targeted to liver are feasible approaches to treat MNGIE. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.217DOI Listing

A Bicistronic Adenoviral Vector Carrying Cytosine Deaminase and Granulocyte-Macrophage Colony-Stimulating Factor Increases the Therapeutic Efficacy of Cancer Gene Therapy.

Hum Gene Ther 2019 Apr 23. Epub 2019 Apr 23.

2 Deparment of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey.

The combination of cytotoxic treatment modalities, including oncolytic viral gene therapies and immunotherapy, usually yields a synergistic effect. In the current study, a bicistronic adenoviral vector, Ad-CD-GMCSF, carrying the cytosine deaminase (CD) and granulocyte-macrophage colony-stimulating factor (GM-CSF) transcription units driven by a cytomegalovirus promoter was constructed, and the efficacy of the vector was tested in tumor cell lines and a syngeneic mouse model of colon cancer. The tumor cells infected with Ad-CD-GMCSF vector were found to produce a substantial amount of GM-CSF in tumor cell lines. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/hum.2018.245
Publisher Site
http://dx.doi.org/10.1089/hum.2018.245DOI Listing
April 2019
6 Reads

A Birds-Eye View: An Interview with Nick Leschly.

Authors:
James M Wilson

Hum Gene Ther Clin Dev 2019 Mar;30(1):5-6

Editor, Human Gene Therapy Clinical Development.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2019.29044.intDOI Listing

Re: Song et al., Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice. Hum Gene Ther Clin Dev 2018; 29(4):188-197.

Hum Gene Ther Clin Dev 2019 Mar;30(1):40

Nuffield Laboratory of Ophthalmology, University of Oxford and Oxford NIHR Biomedical Research Centre, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2019.29041.remDOI Listing

Gene Therapy Briefs.

Authors:
Alex Philippidis

Hum Gene Ther Clin Dev 2019 Mar;30(1):1-4

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2019.29043.bfsDOI Listing

Safety and toxicology of ocular gene therapy with recombinant AAV Vector rAAV.hCNGA3 in non-human primates.

Hum Gene Ther Clin Dev 2019 Mar 13. Epub 2019 Mar 13.

Tuebingen, Germany ;

The purpose of this study was to examine the toxicity and side effects of a recombinant AAV8 vector, aimed to treat CNGA3-linked achromatopsia, after a single subretinal administration in cynomolgus macaques. Animals were followed in two studies: a 13-week study with 22 animals and a 28-day study with 12 animals. Both groups were divided into subgroups receiving either vehicle only, a low (1x1011 vector genomes (vg)), or a high dose (1x1012 vg) of rAAV. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2018.188DOI Listing

Active Immunoprophylaxis and Vaccine Augmentations Mediated by a Novel Plasmid DNA Formulation.

Hum Gene Ther 2019 Apr;30(4):523-533

1 Inovio Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania.

Plasmid DNA (pDNA) gene delivery is a highly versatile technology that has the potential to address a multitude of unmet medical needs. Advances in pDNA delivery to host tissue with the employment of in vivo electroporation (EP) have led to significantly enhanced gene expression and the recent demonstration of clinical efficacy with the platform. Building upon this platform, this study reports that enzyme-mediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to enhance both local and systemic gene expression further. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.241DOI Listing

Hepatotoxicity and Toxicology of In Vivo Lentiviral Vector Administration in Healthy and Liver-Injury Mouse Models.

Hum Gene Ther Clin Dev 2019 Apr 11. Epub 2019 Apr 11.

1 Midwest Fetal Care Center, Children's Hospital of Minnesota, Minneapolis, Minnesota; Minneapolis, Minnesota.

General safety and toxicology assessments supporting in vivo lentiviral vector-based therapeutic development are sparse. We have previously demonstrated the efficacy of a lentiviral vector expressing fumarylacetoacetate hydrolase (LV-FAH) to cure animal models of hereditary tyrosinemia type 1. Therefore, we performed a complete preclinical toxicological evaluation of LV-FAH, in a large cohort (n = 20/group) of wildtype mice and included matched groups of N-nitrosodiethylamine/carbon tetrachloride (DEN/CCl)-induced liver injury mice to assess specific toxicity in fibrotic liver tissue. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2018.249DOI Listing
April 2019
2 Reads

Enhanced Transduction of Hematopoietic Cells with Chimeric Lentiviral Vectors.

Hum Gene Ther 2019 Apr 16. Epub 2019 Apr 16.

1 Division of Innovative Therapies, UMR E007, Institute of Biology François Jacob, CEA, Paris-Sud University, Paris-Saclay University, Fontenay aux Roses, France; Department of Medicine, Brigham and Women's Hospital, Boston Massachusetts.

Recent marketing approval for genetically engineered hematopoietic stem and T cells bears witness to the substantial improvements in lentiviral vectors over the last two decades, but evaluations of the long-term efficacy and toxicity of gene and cell therapy products will, nevertheless, require further studies in nonhuman primate models. monkeys from Mauritius have a low genetic diversity and are particularly useful for reproducible drug testing. In particular, they have a genetically homogeneous class I major histocompatibility complex system that probably mitigates the variability of the response to simian immunodeficiency virus infection. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.179DOI Listing
April 2019
1 Read

Therapeutic delivery of miR-143 targeting tumor metabolism in poorly differentiated thyroid cancer xenografts and efficacy evaluation using 18F-FDG microPET-CT.

Hum Gene Ther 2019 Mar 8. Epub 2019 Mar 8.

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, shanghai, China ;

Poorly differentiated thyroid carcinoma cells tend to be more aggressive and show enhanced glucose uptake which could be exploited for anti-cancer strategy. Previously, we identified hexokinase2 (HK2) as a direct target of miR-143. In our current study, the effects of miR-143 on glucose metabolism and tumor biological behavior were investigated in FTC-133 cells which is a poorly differentiated thyroid carcinoma (PDTC). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.160DOI Listing

Gene Delivery for Limb-Girdle Muscular Dystrophy Type 2D by Isolated Limb Infusion.

Hum Gene Ther 2019 Apr 19. Epub 2019 Apr 19.

1 Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.

In a previous limb-girdle muscular dystrophy type 2D (LGMD2D) clinical trial, robust alpha-sarcoglycan gene expression was confirmed following intramuscular gene () transfer. This paved the way for first-in-human isolated limb infusion (ILI) gene transfer trial to the lower limbs. Delivery of scAAVrh74. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/hum.2019.006
Publisher Site
http://dx.doi.org/10.1089/hum.2019.006DOI Listing
April 2019
8 Reads

Five Years of Successful Inducible Transgene Expression Following Locoregional Adeno-Associated Virus Delivery in Nonhuman Primates with no Detectable Immunity.

Hum Gene Ther 2019 Apr 16. Epub 2019 Apr 16.

1 INSERM UMR 1089, Translational Gene Therapy for Genetic Diseases, Université de Nantes, Nantes, France; and PAnTher, Oniris, Nantes, France.

Anti-transgene immune responses elicited after intramuscular (i.m.) delivery of recombinant adeno-associated virus (rAAV) have been shown to hamper long-term transgene expression in large-animal models of rAAV-mediated gene transfer. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.234DOI Listing
April 2019
3.755 Impact Factor

Dysregulated Expression of microRNA-21 and Disease-Related Genes in Human Patients and in a Mouse Model of Alport Syndrome.

Hum Gene Ther 2019 Mar 29. Epub 2019 Mar 29.

2 Rare Disease Research, Sanofi Genzyme, Framingham, Massachusetts.

Alport syndrome is a genetic disease caused by mutations in type IV collagen and is characterized by progressive kidney disease. The Col4α3 mouse model recapitulates the main features of human Alport syndrome. Previously, it was reported that kidney microRNA-21 (miR-21) expression is significantly increased in Col4α3 mice, and administration of anti-miR-21 oligonucleotides (anti-miR-21) attenuates kidney disease progression in Col4α3 mice, indicating that miR-21 is a viable therapeutic target for Alport syndrome. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.205DOI Listing
March 2019
3 Reads

XVIIth International Parvovirus Workshop.

Hum Gene Ther 2019 Mar 26;30(3):252-256. Epub 2019 Feb 26.

2 Division of Cellular and Molecular Therapy, Departments of Pediatrics and Molecular Genetics and Microbiology, Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2019.29084.mamDOI Listing

Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease.

Hum Gene Ther 2019 Apr 5. Epub 2019 Apr 5.

1 Division of Medical Genetics, Department of Pediatrics, Duke University Medical School, Durham, North Carolina.

Gene therapy for Pompe disease with adeno-associated virus (AAV) vectors has advanced into early phase clinical trials; however, the paucity of cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle, where it is needed to take up acid α-glucosidase (GAA), has impeded the efficacy of Pompe disease gene therapy. Long-acting selective β2 receptor agonists previously enhanced the CI-MPR expression in muscle. In this study we have evaluated the selective β2 agonist salmeterol in GAA knockout mice in combination with an AAV vector expressing human GAA specifically in the liver. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.197DOI Listing
April 2019
1 Read

New Human Chromosomal Sites with "Safe Harbor" Potential for Targeted Transgene Insertion.

Hum Gene Ther 2019 Mar 28. Epub 2019 Mar 28.

1 Department of Pathology and University of Washington, Seattle, Washington.

This study identified 35 new sites for targeted transgene insertion that have the potential to serve as new human genomic "safe harbor" sites (SHS). SHS potential for these 35 sites, located on 16 chromosomes, including both arms of the human X chromosome, and for the existing human SHS AAVS1, hROSA26, and CCR5 was assessed using eight different desirable, widely accepted criteria for SHS verifiable with human genomic data. Three representative newly identified sites on human chromosomes 2 and 4 were then experimentally validated by in vitro and in vivo cleavage-sensitivity tests, and analyzed for population-level and cell line-specific sequence variants that might confound site targeting. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.169DOI Listing
March 2019
7 Reads

CAR T Cells Generated Using Sleeping Beauty Transposon Vectors and Expanded with an EBV-Transformed Lymphoblastoid Cell Line Display Antitumor Activity In Vitro and In Vivo.

Hum Gene Ther 2019 Apr;30(4):511-522

1 Molecular Carcinogenesis Program, National Cancer Institute (INCA), Rio de Janeiro, Brazil.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of cancer is now an approved treatment for B cell malignancies. However, the use of viral vectors to provide long-term CAR expression is associated with high production costs and cumbersome quality controls, impacting the final cost of CAR T cell therapies. Nonviral integrative vectors, such as Sleeping Beauty (SB) transposons, provide an alternative to modify primary T cells. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/hum.2018.218
Publisher Site
http://dx.doi.org/10.1089/hum.2018.218DOI Listing
April 2019
3 Reads

Single Plasmid-Based, Upgradable, and Backward-Compatible Adenoviral Vector Systems.

Hum Gene Ther 2019 Mar 27. Epub 2019 Mar 27.

2 State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, P.R. China; and Weifang Medical University, Weifang, P.R. China.

Existing adenoviral vector systems have two drawbacks. It is labor-intensive and time-consuming to load a transgene in these systems, and transgene-harboring vectors are dead ends: they cannot be reused to construct a vector carrying another transgene or achieving new characteristics. To conquer these shortcomings, single plasmid-based adenoviral vector systems were constructed where a unique PmeI site was located at the position for insertion of the exogenous gene. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.258DOI Listing
March 2019
3 Reads

Sequential Bone-Marrow Cell Delivery of VEGFA/S1P Improves Vascularization and Limits Adverse Cardiac Remodeling After Myocardial Infarction in Mice.

Hum Gene Ther 2019 Mar 27. Epub 2019 Mar 27.

1 Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.

Microvascular dysfunction and resulting tissue hypoxia is a major contributor to the pathogenesis and evolution of cardiovascular diseases (CVD). Diverse gene and cell therapies have been proposed to preserve the microvasculature or boost angiogenesis in CVD, with moderate benefit. This study tested in vivo the impact of sequential delivery by bone-marrow (BM) cells of the pro-angiogenic factors vascular endothelial growth factor (VEGFA) and sphingosine-1-phosphate (S1P) in a myocardial infarction model. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.194DOI Listing
March 2019
1 Read

Lentiviral Gene Therapy for Bone Repair Using Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells.

Hum Gene Ther 2019 Apr 22. Epub 2019 Apr 22.

Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.

Umbilical cord blood (UCB) has been increasingly explored as an alternative source of stem cells for use in regenerative medicine due to several advantages over other stem-cell sources, including the need for less stringent human leukocyte antigen matching. Combined with an osteoinductive signal, UCB-derived mesenchymal stem cells (MSCs) could revolutionize the treatment of challenging bone defects. This study aimed to develop an regional gene-therapy strategy using -transduced allogeneic UCB-MSCs to promote bone repair. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.054DOI Listing
April 2019
2 Reads

RNAi therapy for Machado-Joseph disease: long-term safety profile of lentiviral vectors encoding shRNAs targeting mutant ataxin-3.

Hum Gene Ther 2019 Feb 14. Epub 2019 Feb 14.

University of Coimbra, CNC - Center for Neuroscience and Cell Biology , Rua Larga; , Coimbra, Portugal , Coimbra.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly-inherited neurodegenerative disorder caused by the over-repetition of a CAG codon in the MJD1 gene. This expansion translates into a long polyglutamine tract that confers a toxic gain-of-function to the mutant protein - ataxin-3, leading to neurodegeneration in specific brain regions. No treatment able to modify the disease progression is available. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.157DOI Listing
February 2019
1 Read

The Year in Review: The Top Five Papers of 2018.

Authors:
Terence R Flotte

Hum Gene Ther 2018 Dec;29(12):1339-1340

Editor-in-Chief.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.29079.trfDOI Listing
December 2018

What the Gene Therapy Community Should Do About Sexual Harassment.

Hum Gene Ther 2019 Mar;30(3):249-251

2 Editor-in-Chief.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2019.028DOI Listing

Upregulation of DNA Metabolism-Related Genes Contributes to Radioresistance of Glioblastoma.

Hum Gene Ther Clin Dev 2019 Mar 11. Epub 2019 Mar 11.

Institute of Radiation Medicine, Fudan University, Shanghai, China.

Glioblastomas (GBMs) are the most prevalent brain tumor and exhibit poor prognosis. Radiotherapy is an important strategy for GBMs patients; however, this care remains palliative because of GBMs' radioresistance. Glioma stem cells (GSCs), as a subpopulation residing at the apex of the hierarchy, have been believed to be a pivotal population in radioresistance and recurrence of GBMs. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2018.251DOI Listing
March 2019
5 Reads

A "Hibernating-Like" Viable State Induced by Lentiviral Vector-Mediated Pigment Epithelium-Derived Factor Overexpression in Rat Acute Ischemic Myocardium.

Hum Gene Ther 2019 Mar 29. Epub 2019 Mar 29.

1 Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, P.R. China.

The failure to maintain the viability of ischemic myocardium is one of the mechanisms that causes ischemic heart dysfunction after revascularization. Hibernating myocardium is considered to be able to maintain long-term viability during chronic hypoperfusion. Pigment epithelium-derived factor (PEDF) decreases the contractility of hypoxic cardiomyocytes and protects cardiomyocytes against ischemic injury, which is strikingly similar to the pathophysiologic characteristics of hibernating myocardium. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.186DOI Listing
March 2019
2 Reads

Preclinical Assessment of Suitable Natural Killer Cell Sources for Chimeric Antigen Receptor Natural Killer-Based "Off-the-Shelf" Acute Myeloid Leukemia Immunotherapies.

Hum Gene Ther 2019 Apr 18;30(4):381-401. Epub 2019 Mar 18.

3 Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.

The introduction of chimeric antigen receptors (CARs) to augment the anticancer activity of immune cells represents one of the major clinical advances in recent years. This work demonstrates that sorted CAR natural killer (NK) cells have improved antileukemia activity compared to control NK cells that lack a functional CAR. However, in terms of viability, effectiveness, risk of side effects, and clinical practicality and applicability, an important question is whether gene-modified NK cell lines represent better CAR effector cells than primary human donor CAR-NK (CAR-dNK) cells. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/hum.2018.247
Publisher Site
http://dx.doi.org/10.1089/hum.2018.247DOI Listing
April 2019
5 Reads

Innovative Curative Treatment of Beta Thalassemia: Cost-Efficacy Analysis of Gene Therapy Versus Allogenic Hematopoietic Stem-Cell Transplantation.

Hum Gene Ther 2019 Mar 22. Epub 2019 Mar 22.

1 URC Eco, Assistance Publique-Hôpitaux de Paris, Paris, France; Henri Mondor Teaching Hospital, Créteil, France.

Seventy-five percent of patients with beta thalassemia (β-thalassemia) do not have human leukocyte antigen-matched siblings and until recently had no access to a curative treatment. Gene therapy is a promising treatment that can be proposed to these patients. This study estimates its cost and efficacy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.178DOI Listing
March 2019
2 Reads

Optimization of Dexamethasone Administration for Maintaining Global Transduction Efficacy of Adeno-Associated Virus Serotype 9.

Hum Gene Ther 2019 Mar 11. Epub 2019 Mar 11.

1 Gene Therapy Center, Departments of University of Pittsburgh, Pittsburgh, Pennsylvania.

Glucocorticoids have been commonly used in clinic for their anti-inflammatory and immunosuppressive effects, and it has been proposed that they be used to prevent liver toxicity when systemic administration of adeno-associated virus (AAV) vectors is needed in patients with central nervous system diseases and muscular disorders. Glucocorticoids also enable modulation of vascular permeability. First, this study investigated the impact of dexamethasone on AAV vascular permeability after systemic injection. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.233DOI Listing
March 2019
3 Reads

A Gene Therapy Approach to Improve Copper Metabolism and Prevent Liver Damage in a Mouse Model of Wilson Disease.

Hum Gene Ther Clin Dev 2019 Mar 25;30(1):29-39. Epub 2019 Feb 25.

Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Wilson disease (WD), an autosomal recessive disease caused by mutations in a copper-transporting P-type ATPase (Atp7b), causes severe liver damage. This disease is currently treated with the lifelong use of copper chelation therapy, which has side effects and does not fix copper metabolism. Here, we thoroughly characterized a mouse model of WD, the toxic milk mouse, and used the model to test a gene therapy approach for treating WD. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2018.219DOI Listing
March 2019
1 Read

Preclinical Evaluation of Chimeric Antigen Receptor-Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer.

Hum Gene Ther 2019 Apr 13;30(4):402-412. Epub 2019 Mar 13.

1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.

Chimeric antigen receptor-modified T cells (CAR-T cells) have emerged as a promising cancer immunotherapy for solid tumors. Epithelial cell adhesion molecule (EpCAM) is overexpressed in a variety of tumors and is recognized as a biomarker for circulating tumor cells and cancer stem cells, representing an attractive target for adoptive T-cell immunotherapy. This study generated third-generation CAR-T cells with redirected specificity to EpCAM (EpCAM CAR-T) by lentiviral vector. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/hum.2018.229
Publisher Site
http://dx.doi.org/10.1089/hum.2018.229DOI Listing
April 2019
40 Reads
3.755 Impact Factor

Effect of Genetic Modifications on Physical and Functional Titers of Adenoviral Cancer Gene Therapy Constructs.

Hum Gene Ther 2019 Feb 28. Epub 2019 Feb 28.

1 Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; Helsinki University Hospital, Helsinki, Finland.

After the discovery and characterization of the adenovirus in the 1950s, this prevalent cause of the common cold and other usually mild diseases has been modified and utilized in biomedicine in several ways. To date, adenoviruses are the most frequently used vectors and therapeutic (e.g. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.240DOI Listing
February 2019
1 Read

Questions Answered and Unanswered by the First CRISPR Editing Study in a Canine Model of Duchenne Muscular Dystrophy.

Hum Gene Ther 2019 Feb 26. Epub 2019 Feb 26.

1 Department of Molecular Microbiology and Immunology and National Institutes of Health, Rockville, Maryland.

Clustered regularly interspaced short palindromic repeats (CRISPR) editing is being considered as a potential gene repair therapy to treat Duchenne muscular dystrophy, a dystrophin-deficient lethal muscle disease affecting all muscles in the body. A recent preliminary study from the Olson laboratory (Amoasii et al. Science 2018;362:89-91) showed robust dystrophin restoration in a canine Duchenne muscular dystrophy model following intramuscular or intravenous delivery of the CRISPR editing machinery by adeno-associated virus serotype 9. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.243DOI Listing
February 2019
1 Read
3.755 Impact Factor

Urocortin 2 Gene Transfer Reduces the Adverse Effects of a Western Diet on Cardiac Function in Mice.

Hum Gene Ther 2019 Mar 11. Epub 2019 Mar 11.

1 Veterans Affairs San Diego Healthcare System, San Diego, California; and University of California San Diego, San Diego, California.

Diabetes mellitus is associated with increased risk of heart failure. It has been previously demonstrated in mice that a single injection of adeno-associated virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal in models of insulin resistance and improves the function of the failing heart. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/hum.2018.150
Publisher Site
http://dx.doi.org/10.1089/hum.2018.150DOI Listing
March 2019
10 Reads

Cardiac-Directed Expression of Adenylyl Cyclase Catalytic Domain (C1C2) Attenuates Deleterious Effects of Pressure Overload.

Hum Gene Ther 2019 Mar 8. Epub 2019 Mar 8.

1 Veterans Affairs San Diego Healthcare System, San Diego, California, and University of California San Diego, San Diego, California.

A fusion protein (C1C2) constructed by fusing the intracellular C1 and C2 segments of adenylyl cyclase type 6 (AC6) retains beneficial effects of AC6 expression, without increasing cyclic adenosine monophosphate generation. The effects of cardiac-directed C1C2 expression in pressure overload is unknown. Left ventricular (LV) pressure overload was induced by transverse aortic constriction (TAC) in C1C2 mice and in transgene negative (TG-) mice. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/hum.2018.176
Publisher Site
http://dx.doi.org/10.1089/hum.2018.176DOI Listing
March 2019
17 Reads

(Pro)renin Receptor RNAi Silencing Attenuates Diabetic Cardiomyopathy Pathological Process in Rats.

Hum Gene Ther 2019 Jan 11. Epub 2019 Jan 11.

Department of Cardiology and Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University,, Jinan, Shandong, China.

(Pro) renin receptor (PRR) is a novel component of the renin-angiotensin system (RAS) that has been demonstrated to be involved in cardiovascular diseases. Recent research reported that diabetic cardiomyopathy (DCM) may be accompanied by high expression of PRR, indicating that PRR may be a potential therapeutic target for DCM. However, the exact mechanisms of PRR in DCM have not been completely clarified. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.155DOI Listing
January 2019
2 Reads

Knockdown of LINC02465 Suppresses Gastric Cancer Cell Growth and Metastasis Via PI3K/AKT Pathway.

Hum Gene Ther Clin Dev 2019 Mar 7;30(1):19-28. Epub 2019 Feb 7.

Department of Gastroenterology, First People's Hospital of Yancheng City, Yancheng, Jiangsu Province, China.

Gastric cancer (GC) is the second primary cause of cancer-associated mortality around the world. Long noncoding RNAs (lncRNAs) are critical modulators of multiple cellular processes, and their abnormal expression and/or function are related to a variety of diseases, including cancer. Various lncRNAs have been shown to exert a functional role in GC, but more still remain to be identified, since the therapies for GC patients are limited. Read More

View Article

Download full-text PDF

Source
https://www.liebertpub.com/doi/10.1089/humc.2018.177
Publisher Site
http://dx.doi.org/10.1089/humc.2018.177DOI Listing
March 2019
11 Reads

Top Five Gene Therapy Stories of 2019.

Authors:
Terence R Flotte

Hum Gene Ther 2019 Jan;30(1):1-2

Editor-in-Chief.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.29080.trfDOI Listing
January 2019
1 Read

In Vitro and Clinical Studies of Gene Therapy with Recombinant Human Adenovirus-p53 Injection for Malignant Melanoma.

Hum Gene Ther Clin Dev 2019 Mar 31;30(1):7-18. Epub 2019 Jan 31.

1 State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.

Malignant melanoma is an aggressive tumor with high fatality rates and poor prognosis, mainly due to the lack of efficient treatment methods. The present study investigated the potential antitumor effects of recombinant adenovirus p53 (rAd-p53) on human malignant melanoma. The optimal viral titer on a human malignant melanoma (A-375) cell line was determined for the rAd-p53 treatment. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2018.112DOI Listing
March 2019
8 Reads

Basic and Clinical Application of Adeno-Associated Virus-Mediated Genome Editing.

Hum Gene Ther 2019 Feb 28. Epub 2019 Feb 28.

School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, P.R. China.

Traditional gene therapy (gene replacement) has made a breakthrough in treating inherited diseases. Adeno-associated virus (AAV) has emerged as a highly promising vector with innate ability, boosting the development of gene replacement and gene targeting. With the recent advance of engineered nucleases that work efficiently in human cells, AAV mediated-genome editing with nucleases has raised hopes for in situ gene therapy of inherited and non-inherited diseases. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.190DOI Listing
February 2019
1 Read

Validation and Safety of Visual Restoration by Ectopic Expression of Human Melanopsin in Retinal Ganglion Cells.

Hum Gene Ther 2019 Feb 28. Epub 2019 Feb 28.

1 Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, P.R. China; and Chongqing, P.R. China.

To study whether ectopic human melanopsin (hMel) in retinal ganglion cells (RGCs) could restore the visual function in end-stage retinal degeneration, AAV2/8-CMV-hMel/FYP was injected into the intravitreal space of Royal College of Surgeons (RCS) rats. It was observed that ectopic hMel/yellow fluorescent protein (YFP) was dominantly expressed in the RGCs of the RCS rat retinae. At 30-45 days after administration of AAV2/8-CMV-hMel/FYP in RCS rats, the flash visual evoked potentials and behavioral results demonstrated that visual function was significantly improved compared to that in the control group, while no improvement in flash electroretinography was observed at this time point. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/hum.2018.009DOI Listing
February 2019
3 Reads

Gene Therapy Entering the Land of Oz.

Authors:
James M Wilson

Hum Gene Ther Clin Dev 2018 12;29(4):171

Editor, Human Gene Therapy Clinical Development.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/humc.2018.29040.wilDOI Listing
December 2018
1 Read