4,225 results match your criteria Human Gene Therapy [Journal]


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

Hum Gene Ther 2019 Feb 16. Epub 2019 Feb 16.

Keck School of Medicine of the University of Southern California, 12223, Department of Orthopaedic Surgery , 1520 San Pablo Street , Suite 2000 , Los Angeles, California, United States , 90033 ;

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 HLA matching. Combined with an osteoinductive signal, UCB-MSCs could revolutionize the treatment of challenging bone defects. In this study we aimed to develop an ex vivo regional gene therapy strategy using BMP-2-transduced allogeneic UCB-MSCs to promote bone repair. Read More

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http://dx.doi.org/10.1089/hum.2018.054DOI Listing
February 2019

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

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

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.

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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 Feb 13. Epub 2019 Feb 13.

University of Massachusetts Medical School, Pediatrics , 55 Lake Avenue North , S1-340 , Worcester, Massachusetts, United States , 01655 ;

N/A. Read More

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http://dx.doi.org/10.1089/hum.2019.028DOI Listing
February 2019

Upregulation of DNA metabolism-related genes contributes to radioresistance of glioblastoma.

Hum Gene Ther Clin Dev 2019 Feb 12. Epub 2019 Feb 12.

Institute of Radiation Medicine, Fudan University , No. 2094 Xietu Road , Shanghai , Shanghai, China , 200032 ;

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

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http://dx.doi.org/10.1089/humc.2018.251DOI Listing
February 2019

A "Hibernating-like" viable state induced by Lentiviral Vector-Mediated PEDF overexpression in rat acute ischemic myocardium.

Hum Gene Ther 2019 Feb 8. Epub 2019 Feb 8.

Zzm666666xuzhou, China , 221000 ;

Background The failure to maintain the viability of ischemic myocardium is one of the mechanisms causing ischemic heart dysfunction after revascularization. Hibernating Myocardium is considered to be able to maintain a 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

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http://dx.doi.org/10.1089/hum.2018.186DOI Listing
February 2019

Preclinical assessment of suitable natural killer (NK) cell sources for chimeric antigen receptor (CAR)-NK-based "off-the-shelf" AML immunotherapies.

Hum Gene Ther 2019 Feb 8. Epub 2019 Feb 8.

Hannover Medical School, Experimental Hematology , Carl-Neuberg-Str. 1 , Hannover, Germany , 36025 ;

The introduction of chimeric antigen receptors (CARs) to augment the anti-cancer activity of immune cells represents one of the major clinical advances in recent years. In this work, we demonstrate that sorted CAR-NK cells have improved anti-leukemia activity as 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

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https://www.liebertpub.com/doi/10.1089/hum.2018.247
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http://dx.doi.org/10.1089/hum.2018.247DOI Listing
February 2019
1 Read

Innovative curative treatment of βeta-thalassemia: cost-efficacy analysis of gene therapy versus allogenic hematopoietic stem cell transplantation.

Hum Gene Ther 2019 Jan 31. Epub 2019 Jan 31.

Assistance Publique - Hopitaux de Paris, 26930, Urc-Eco, Paris, Île-de-France, France ;

Background Seventy-five percent of βeta-thalassemic patients do not have Human Leukocyte Antigen (HLA) matched siblings and had until recently 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. Methods We compared in a mono-centric retrospective study and cost-efficacy analysis the two-year outcomes and costs of β-thalassemic patients treated by gene therapy and HSCT. Read More

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http://dx.doi.org/10.1089/hum.2018.178DOI Listing
January 2019

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

Hum Gene Ther 2019 Jan 31. Epub 2019 Jan 31.

University of North Carolina at Chapel Hill, 2331, gene therapy center , 104 Manning Dr , Thurston Building , Chapel Hill, North Carolina, United States , 27515 ;

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

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http://dx.doi.org/10.1089/hum.2018.233DOI Listing
January 2019
1 Read

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 Jan 29. Epub 2019 Jan 29.

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

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 (txJ) mouse, and used the model to test a gene therapy approach for treating WD. Read More

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

Preclinical evaluation of chimeric antigen receptor-modified T cells specific to EpCAM for treating colorectal cancer.

Hum Gene Ther 2019 Jan 29. Epub 2019 Jan 29.

State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, P.R. China. , State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, P.R. China , chengdu, China , 610041 ;

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 recognized as a biomarker for circulating tumor cells (CTCs) and cancer stem cells (CSCs), representing an attractive target for adoptive T cell immunotherapy. In the current study, we generated a third generation CAR-T cells with redirected specificity to EpCAM (EpCAM CAR-T) by lentiviral vector. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.229
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http://dx.doi.org/10.1089/hum.2018.229DOI Listing
January 2019
13 Reads
3.755 Impact Factor

Effect of genetic modifications on physical and functional titers of adenoviral cancer gene therapy constructs.

Hum Gene Ther 2019 Jan 23. Epub 2019 Jan 23.

University of Helsinki, Cancer Gene Therapy Group, Faculty of Medicine, Helsinki, Finland.

After 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

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

Questions answered and unanswered by the first CRISPR editing study in the canine model of Duchenne muscular dystrophy.

Hum Gene Ther 2019 Jan 16. Epub 2019 Jan 16.

University of missouri, Molecular microbiology and Immunology , M610 Med Sci Bldg , columbia, Missouri, United States , 65212 ;

CRISPR editing is being considered as a potential gene repair therapy to treat Duchenne muscular dystrophy (DMD), a dystrophin-deficient lethal muscle disease affecting all muscles in the body. A recent preliminary study from the Olson laboratory (Amoasii et al. 2018 Science 362:89-91) showed robust dystrophin restoration in a canine DMD model following intramuscular or intravenous delivery of the CRISPR editing machinery by adeno-associated virus serotype-9 (AAV9). Read More

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http://dx.doi.org/10.1089/hum.2018.243DOI Listing
January 2019

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

Hum Gene Ther 2019 Jan 16. Epub 2019 Jan 16.

VA San Diego Healthcare System , 3350 La Jolla Village Drive , San Diego, California, United States , 92161.

Background: Diabetes mellitus is associated with increased risk of heart failure. We 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 function of the failing heart. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.150
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http://dx.doi.org/10.1089/hum.2018.150DOI Listing
January 2019
4 Reads

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

Hum Gene Ther 2019 Jan 14. Epub 2019 Jan 14.

VA San Diego Healthcare System, San Diego, California, United States.

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 cAMP generation. The effects of cardiac-directed C1C2 expression in pressure-overload is unknown. LV pressure overload was induced by transverse aortic constriction (TAC) in C1C2 mice and in transgene negative (TG-) mice. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.176
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http://dx.doi.org/10.1089/hum.2018.176DOI Listing
January 2019
5 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

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

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

Hum Gene Ther Clin Dev 2019 Feb 7. 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

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https://www.liebertpub.com/doi/10.1089/humc.2018.177
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http://dx.doi.org/10.1089/humc.2018.177DOI Listing
February 2019
5 Reads

Top Five Gene Therapy Stories of 2019.

Authors:
Terence R Flotte

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

Editor-in-Chief.

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

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

Hum Gene Ther Clin Dev 2019 Jan 31. 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

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http://dx.doi.org/10.1089/humc.2018.112DOI Listing
January 2019
3 Reads

Basic and clinical application of adeno-associated virus-mediated genome editing.

Hum Gene Ther 2018 Dec 27. Epub 2018 Dec 27.

Wenzhou Medical University, 26453, School of Ophthalmology and Optometry , West Xue Yuan Road , Wenzhou, China , 325035 ;

Traditional gene therapy (gene replacement), as the most compelling concepts in clinical medicine, have gained 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 have raised hopes for the gene therapy of inherited or non-inherited diseases. Read More

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http://dx.doi.org/10.1089/hum.2018.190DOI Listing
December 2018

Validation and Safety of visual restoration by ectopic expression of human melanopsin in retinal ganglion cells.

Hum Gene Ther 2018 Dec 22. Epub 2018 Dec 22.

Third Military Medical University Southwest Hospital, 388288, Southwest Eye Hospital, Chongqing, 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. We observed that ectopic hMel/YFP was dominantly expressed in the RGCs of the RCS rat retinae. At 30-45 d after administration of AAV2/8-CMV-hMel/FYP in RCS rats, the FVEP and behavioral results demonstrated that visual function was significantly improved compared with that in the control group, while no improvement in FERG was observed at this time point. Read More

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http://dx.doi.org/10.1089/hum.2018.009DOI Listing
December 2018
2 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.

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

Tachi Yamada: An Academic, Drug Developer and Humanist.

Authors:
James M Wilson

Hum Gene Ther Clin Dev 2018 12;29(4):176-178

Editor, Human Gene Therapy Clinical Development.

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http://dx.doi.org/10.1089/humc.2018.29038.intDOI Listing
December 2018

Gene Therapy Briefs.

Authors:
Alex Philippidis

Hum Gene Ther Clin Dev 2018 12;29(4):172-175

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http://dx.doi.org/10.1089/humc.2018.29039.bfsDOI Listing
December 2018

Traditional Approaches for Company Valuation Are Flawed for Valuing In Vivo Gene Therapy Companies.

Hum Gene Ther Clin Dev 2018 12 14;29(4):179-187. Epub 2018 Dec 14.

Equity Research Department, Chardan, New York, New York.

The era of gene therapy has begun. In recent years, potentially breakthrough datasets and rapidly expanding company pipelines have begun to overshadow the unfulfilled promise characteristic of the gene therapy sector in decades prior. One barometer for progress in the space can be seen in stock markets, where NASDAQ-listed in vivo gene therapy companies we follow have increased from 4 companies with $1. Read More

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http://dx.doi.org/10.1089/humc.2018.29037.gamDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312046PMC
December 2018

Pretreatment of rAAV-Mediated Expression of Myostatin Propeptide Lowers Type 2 Diabetes Incidence in C57BL/6 Mice on a High-Fat Diet.

Hum Gene Ther 2019 Jan 31. Epub 2019 Jan 31.

1 Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders (Huazhong University of Science and Technology), Wuhan, P.R. China.

Myostatin, a negative modulator of muscle growth, has been considered as a potential target for the treatment of type 2 diabetes (T2D). In previous work, it was found that myostatin inhibition by adeno-associated virus (AAV)-mediated gene delivery of myostatin propeptide (MPRO) could improve muscle mass and achieve therapeutic effects on glucose regulation and lipid metabolism in db/db mice. This study investigated whether pre-intervention of rAAV-mediated expression of MPRO could lower the incidence of T2D. Read More

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http://dx.doi.org/10.1089/hum.2018.140DOI Listing
January 2019
2 Reads

Long-Term Effects of Gene Therapy in a Novel Mouse Model of Human MFRP-Associated Retinopathy.

Hum Gene Ther 2019 Jan 16. Epub 2019 Jan 16.

1 Shiley Eye Institute, University of California San Diego, La Jolla, California.

Patients harboring homozygous c.498_499insC mutations in MFRP demonstrate hyperopia, microphthalmia, retinitis pigmentosa, retinal pigment epithelial atrophy, variable degrees of foveal edema, and optic disc drusen. The disease phenotype is variable, however, with some patients maintaining good central vision and cone function till late in the disease. Read More

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http://dx.doi.org/10.1089/hum.2018.192DOI Listing
January 2019
1 Read

Preclinical Safety Evaluation of Oncolytic Herpes Simplex Virus Type 2.

Hum Gene Ther 2019 Jan 16. Epub 2019 Jan 16.

1 National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Centre of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, P.R. China.

Oncolytic virotherapy is a new and safe therapeutic strategy based on the inherent cytotoxicity of oncolytic viruses and their ability to replicate and spread within tumors in a selective manner. In a previous study, a new type of oncolytic herpes simplex virus type 2 (oHSV-2, named OH2) was constructed to treat human cancers. That study demonstrated that OH2 is genetically and biologically stable. Read More

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http://dx.doi.org/10.1089/hum.2018.170DOI Listing
January 2019
14 Reads

STAT3-activated lncRNA LUCAT1 drives cell proliferation, migration and invasion in hepatoblastoma through regulating miR-301b/STAT3 axis.

Hum Gene Ther 2018 Nov 27. Epub 2018 Nov 27.

Beijing, China ;

Hepatoblastoma usually occurs in infant or toddlers. Nowadays, long non-coding RNAs (lncRNAs) have been widely studied in various human cancers. However, the role of lncRNAs in hepatoblastoma still needs to be elucidated. Read More

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http://dx.doi.org/10.1089/hum.2018.146DOI Listing
November 2018
1 Read

Synergistic Antitumor Effect on Bladder Cancer by Rational Combination of Programmed Cell Death 1 Blockade and CRISPR-Cas9-Mediated Long Non-Coding RNA Urothelial Carcinoma Associated 1 Knockout.

Hum Gene Ther 2018 Dec 19;29(12):1352-1363. Epub 2018 Nov 19.

1 Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, P.R. China.

Targeted therapy produces objective responses in bladder cancer patients, although the responses can be short. Meanwhile, response rates to immune therapy are lower, but the effects are more durable. Based on these findings, it was hypothesized that urothelial carcinoma associated 1 (UCA1)-targeted therapy could synergize with programmed cell death 1 (PD-1) blockade to enhance antitumor activity. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.048
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http://dx.doi.org/10.1089/hum.2018.048DOI Listing
December 2018
11 Reads

Establishment of a High-Yield Recombinant Adeno-Associated Virus/Human Bocavirus Vector Production System Independent of Bocavirus Nonstructural Proteins.

Hum Gene Ther 2019 Jan 31. Epub 2019 Jan 31.

1 Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas.

The genome of recombinant adeno-associated virus 2 (rAAV2) remains a promising candidate for gene therapy for cystic fibrosis (CF) lung disease, but due to limitations in the packaging capacity and the tropism of this virus with respect to the airways, strategies have evolved for packaging an rAAV2 genome (up to 5.8 kb) into the capsid of human bocavirus 1 (HBoV1) to produce a chimeric rAAV2/HBoV1 vector. Although a replication-incompetent HBoV1 genome has been established as a trans helper for capsid complementation, this system remains suboptimal with respect to virion yield. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.173
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http://dx.doi.org/10.1089/hum.2018.173DOI Listing
January 2019
11 Reads

Establishing China's National Standard for the Recombinant Adenovirus Type 5 Vector-Based Ebola Vaccine (Ad5-EBOV) Virus Titer.

Hum Gene Ther Clin Dev 2018 12 4;29(4):226-232. Epub 2018 Dec 4.

1 National Institute for Food and Drug Control, Beijing, P.R. China.

The 2014 Ebola outbreak in West Africa brought great threat to public health worldwide. There was no approved antiviral therapy or vaccine available to control the disease at that time. Several kinds of Ebola vaccines were urgently under development across the world. Read More

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http://dx.doi.org/10.1089/humc.2018.129DOI Listing
December 2018
1 Read

An AAV Dual Vector Strategy Ameliorates the Stargardt Phenotype in Adult Abca4 Mice.

Hum Gene Ther 2018 Dec 26. Epub 2018 Dec 26.

1 Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford, United Kingdom .

The recent approval in the United States of the first adeno-associated viral (AAV) vector for the treatment of an inherited retinal degeneration validates this approach for the treatment of many other diseases. A major limiting factor continues to be the size restriction of the AAV transgene at under 5 kb. Stargardt disease is the most prevalent form of recessively inherited blindness and is caused by mutations in ABCA4, the gene that codes for ATP-binding cassette transporter protein family member 4, which has a coding sequence length of 6. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.156
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http://dx.doi.org/10.1089/hum.2018.156DOI Listing
December 2018
15 Reads

Induced CD20 Expression on B-Cell Malignant Cells Heightened the Cytotoxic Activity of Chimeric Antigen Receptor Engineered T Cells.

Hum Gene Ther 2019 Jan 23. Epub 2019 Jan 23.

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

CD20 is an effective immunotherapy target for CD20 B-cell malignant cells. Monoclonal antibody, especially rituximab, has been a conventional strategy in the treatment of B-cell malignancies such as non-Hodgkin's lymphoma. However, treatment with monoclonal antibodies has not been enough to overcome the refractory/relapse problems. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.119
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http://dx.doi.org/10.1089/hum.2018.119DOI Listing
January 2019
15 Reads

LncRNA HOXA-AS2 facilitates tumorigenesis and progression of papillary thyroid cancer through modulating miR-15a-5p/HOXA3 axis.

Hum Gene Ther 2018 Oct 30. Epub 2018 Oct 30.

Shaoxing, China ;

Long non-coding RNA HOXA-AS2 has been found to be an oncogene in several types of human malignant tumors. However, the role HOXA-AS2 in regulating the occurrence and development of papillary thyroid cancer (PTC) is still unclear. This study focused on investigating the function and mechanism of HOXA-AS2 in PTC progression. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.109
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http://dx.doi.org/10.1089/hum.2018.109DOI Listing
October 2018
11 Reads

Ultrasound-Targeted Microbubble Destruction Delivery of Insulin-Like Growth Factor 1 cDNA and Transforming Growth Factor Beta Short Hairpin RNA Enhances Tendon Regeneration and Inhibits Scar Formation In Vivo.

Hum Gene Ther Clin Dev 2018 12 25;29(4):198-213. Epub 2018 Oct 25.

1 Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China.

Ultrasound-targeted microbubble destruction (UTMD), which has been successfully used for the treatment of many diseases, offers a promising noninvasive approach for target-specific gene delivery. This study investigated the UTMD delivery of insulin-like growth factor 1 (IGF-1) cDNA and transforming growth factor beta (TGF-β) short hairpin RNA for Achilles tendon injury in rats. Briefly, 168 rats with an injured Achilles tendon were randomly divided into seven groups: (1) IGF-1 + UTMD, (2) TGF-β + UTMD, (3) IGF-1 + TGF-β + UTMD, (4) control, (5) IGF-1, (6) TGF-β, and (7) IGF-1 + TGF-β. Read More

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http://dx.doi.org/10.1089/humc.2018.121DOI Listing
December 2018

Intrathecal Adeno-Associated Virus Vector-mediated Gene Delivery for Adrenomyeloneuropathy.

Hum Gene Ther 2018 Oct 25. Epub 2018 Oct 25.

Massachusetts General Hospital, Neurology , 55 Fruit Street , Boston, Massachusetts, United States , 02114 ;

Mutations in the gene encoding the peroxisomal ATP binding cassette transporter (ABCD1) cause elevations in very long chain fatty acids (VLCFA) and the neurodegenerative disease adrenoleukodystrophy (ALD). In most adults, this manifests as the spinal cord axonopathy, adrenomyeloneuropathy (AMN). A challenge in virus-based gene therapy in AMN is how to achieve functional gene correction to the entire spinal cord while minimizing leakage into the systemic circulation, which could contribute to toxicity. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.079
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http://dx.doi.org/10.1089/hum.2018.079DOI Listing
October 2018
5 Reads

Somatic Gene Editing of GUCY2D by AAV-CRISPR/Cas9 Alters Retinal Structure and Function in Mouse and Macaque.

Hum Gene Ther 2018 Dec 20. Epub 2018 Dec 20.

1 Department of Ophthalmology, University of Florida, Gainesville, Florida.

Mutations in GUCY2D, the gene encoding retinal guanylate cyclase-1 (retGC1), are the leading cause of autosomal dominant cone-rod dystrophy (CORD6). Significant progress toward clinical application of gene replacement therapy for Leber congenital amaurosis (LCA) due to recessive mutations in GUCY2D (LCA1) has been made, but a different approach is needed to treat CORD6 where gain of function mutations cause dysfunction and dystrophy. The CRISPR/Cas9 gene editing system efficiently disrupts genes at desired loci, enabling complete gene knockout or homology directed repair. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.193
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http://dx.doi.org/10.1089/hum.2018.193DOI Listing
December 2018
16 Reads

Comparison of Dendritic Cell Activation by Virus-Based Vaccine Delivery Vectors Emphasizes the Transcriptional Downregulation of the Oxidative Phosphorylation Pathway.

Hum Gene Ther 2019 Jan 25. Epub 2019 Jan 25.

1 Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece; Democritus University of Thrace, Alexandroupolis, Greece.

Antigen delivery platforms based on engineered viruses or virus-like particles are currently developed as vaccines against infectious diseases. As the interaction of vaccines with dendritic cells (DCs) shapes the immunological response, we compared the interaction of a range of virus-based vectors and virus-like particles with DCs in a murine model of systemic administration and transcriptome analyses of splenic DCs. The transcriptome profiles of DCs separated the vaccine vectors into two distinct groups characterized by high- and low-magnitude differential gene expression, which strongly correlated with (1) the surface expression of costimulatory molecules CD40, CD83, and CD86 on DCs, and (2) antigen-specific T-cell responses. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.161
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http://dx.doi.org/10.1089/hum.2018.161DOI Listing
January 2019
8 Reads

A novel BaEVRless-pseudotyped γ-globin lentiviral vector drives high and stable HbF expression and improves thalassemic erythropoiesis in vitro.

Hum Gene Ther 2018 Oct 16. Epub 2018 Oct 16.

Biomedical Research Foundation of the Academy of Athens, Gene Therapy Lab , 4 Soranou Effessiou St , Athens, Greece , 11527.

We have previously demonstrated that the self-inactivating γ-globin lentiviral vector GGHI can significantly increase HbF in erythroid cells from thalassemia patients and thus improve the disease phenotype in vitro. In the present study, we further improved the GGHI vector by incorporating novel enhancer elements and pseudotyping it also with the baboon endogenous virus envelope glycoprotein BaEVRless, which efficiently and specifically targets human CD34+ cells. We evaluated the hypothesis that the newly constructed vector designated as GGHI-mB-3D, would increase hCD34+ cell tropism and thus the transduction efficiency at low multiplicity of infection, leading to increased transgene expression. Read More

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http://dx.doi.org/10.1089/hum.2018.022DOI Listing
October 2018
1 Read

Thoughts on Chemistry, Manufacturing, and Control of Cell Therapy Products for Clinical Application.

Authors:
Wei Wei Jianhui Luo

Hum Gene Ther 2019 Feb 13;30(2):119-126. Epub 2018 Nov 13.

Center for Drug Evaluation, National Medical Products Administration, Beijing, China.

Cell therapy has emerged as a promising new treatment in medicine, which is expected to be able to cure diseases by repairing, replacing, and regenerating tissues, as well as through immune modulation. However, challenges remain in ensuring consistent quality, clinical efficacy, and safety profiles because of the diversity of cell types and clinical indications for cell therapy products (CTPs), as well as different and complex manufacturing process. Therefore, scientific consensus and regulatory measurements are urgently warranted to promote the translation of the latest scientific advances and innovative manufacturing technologies into clinical application. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.097
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http://dx.doi.org/10.1089/hum.2018.097DOI Listing
February 2019
6 Reads

Varinostat Alters Gene Expression Profiles in Aortic Tissues from ApoE Mice.

Hum Gene Ther Clin Dev 2018 12 12;29(4):214-225. Epub 2018 Nov 12.

1 Department of Cardiology and Beijing Anzhen Hospital and Capital Medical University, Beijing, P.R. China.

Atherosclerosis (AS) is a complex, chronic inflammatory disease that is characterized by plaque buildup within arterial vessel walls. Preclinical trials have suggested that vorinostat, a pan-histone deacetylase inhibitor (HDACi), reduces vascular inflammation and AS, but the underlying protective mechanism has not been fully elucidated. The present study aimed to identify altered gene expression profiles in aortic tissues from ApoE mice after vorinostat treatment. Read More

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https://www.liebertpub.com/doi/10.1089/humc.2018.141
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http://dx.doi.org/10.1089/humc.2018.141DOI Listing
December 2018
18 Reads

Spring Forward: ESGCT Trains the Next Generation of Gene and Cell Therapists.

Hum Gene Ther 2018 Oct;29(10):1074-1075

2 Department of Haematology, University College London Cancer Institute , London, United Kingdom ; and St. Jude Children's Research Hospital , Memphis, Tennessee.

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https://www.liebertpub.com/doi/10.1089/hum.2018.29076.vmw
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http://dx.doi.org/10.1089/hum.2018.29076.vmwDOI Listing
October 2018
6 Reads

Gene and Cell Therapy: Tearing Down Walls.

Hum Gene Ther 2018 Oct;29(10):1071-1073

1 European Editor-Human Gene Therapy; Department of Cardiovascular Sciences, University of Leuven , Leuven, Belgium .

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http://dx.doi.org/10.1089/hum.2018.29074.tvaDOI Listing
October 2018

An Interview with Michele De Luca.

Authors:
Graham C Parker

Hum Gene Ther 2018 Oct;29(10):1076-1082

1 Editor-in-Chief of Stem Cells and Development, Wayne State University School of Medicine , Detroit, Michigan.

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https://www.liebertpub.com/doi/10.1089/hum.2018.29075.mdl
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http://dx.doi.org/10.1089/hum.2018.29075.mdlDOI Listing
October 2018
2 Reads

Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice.

Hum Gene Ther Clin Dev 2018 12;29(4):188-197

1 Applied Genetic Technologies Corporation (AGTC), Alachua, FL.

Applied Genetic Technologies Corporation (AGTC) is developing a recombinant adeno-associated virus (rAAV) vector AGTC-501, also designated AAV2tYF-GRK1-RPGRco, to treat retinitis pigmentosa (RP) in patients with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. The vector contains a codon-optimized human RPGR cDNA (RPGRco) driven by a photoreceptor-specific promoter (G protein-coupled receptor kinase 1, GRK1) and is packaged in an AAV2 capsid with three surface tyrosine residues changed to phenylalanine (AAV2tYF). We conducted a safety and potency study of this vector administered by subretinal a injection in the naturally occurring RPGR-deficient Rd9 mouse model. Read More

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http://dx.doi.org/10.1089/humc.2018.168DOI Listing
December 2018
2 Reads

Efficient reconstitution of hepatic microvasculature by endothelin receptor antagonism in liver sinusoidal endothelial cells.

Hum Gene Ther 2018 Sep 28. Epub 2018 Sep 28.

Albert Einstein College of Medicine, Medicine , Ullmann 625 , 1300 Morris Park Avenue , New York , Bronx, New York, United States , 10461 ;

Reconstitution of healthy endothelial cells in vascular beds offers opportunities for mechanisms in tissue homeostasis, organ regeneration, and correction of deficient functions. Liver sinusoidal endothelial cells express unique functions and their transplantation is relevant for disease models and for cell therapy. As molecular targets for improving transplanted cell engraftment and proliferation will be highly significant, we determined whether ETA/B receptor antagonism by the drug, bosentan, could overcome cell losses due to cell transplantation-induced cytotoxicity. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.166
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http://dx.doi.org/10.1089/hum.2018.166DOI Listing
September 2018
2 Reads

Immunoengineering of the Vascular Endothelium to Silence MHC Expression During Normothermic Ex Vivo Lung Perfusion.

Hum Gene Ther 2018 Nov 20. Epub 2018 Nov 20.

1 Institute of Transfusion Medicine , Hannover Medical School, Hannover, Germany.

Disparities at the major histocompatibility complex (MHC) antigens and associated minor antigens trigger harmful immune responses, leading to graft rejection after transplantation. We showed that MHC-silenced cells and tissues are efficiently protected against rejection. In complex vascularized organs, the endothelium is the major interface between donor and recipient. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.117
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http://dx.doi.org/10.1089/hum.2018.117DOI Listing
November 2018
5 Reads
3.755 Impact Factor

A Phase 1 Trial of Oncolytic Adenovirus ICOVIR-5 Administered Intravenously to Cutaneous and Uveal Melanoma Patients.

Hum Gene Ther 2018 Nov 13. Epub 2018 Nov 13.

3 Department of Medical Oncology, Oncobell Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet , Barcelona, Spain.

Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in the United States and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Read More

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https://www.liebertpub.com/doi/10.1089/hum.2018.107
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http://dx.doi.org/10.1089/hum.2018.107DOI Listing
November 2018
4 Reads