journal
MENU ▼
Read by QxMD icon Read
search

Human Gene Therapy

journal
https://www.readbyqxmd.com/read/28073291/future-of-raav-gene-therapy-platform-for-rnai-gene-editing-and-beyond
#1
Paul Valdmanis, Mark A Kay
The use of recombinant adeno-associated viruses (rAAVs) ushered in a new millennium of gene transfer for therapeutic treatment of a number of conditions including congenital blindness, hemophilia, and spinal muscular atrophy (SMA). rAAV vectors have remarkable staying power from a therapeutic standpoint withstanding several ebbs and flows. As new technologies such as clustered regularly interspaced short palindromic repeat (CRISPR) genome editing emerge, it is now the delivery tool - the AAV vector - that is the stalwart...
January 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28056565/characterization-of-aav-mediated-human-factor-viii-gene-therapy-in-hemophilia-a-mice
#2
Jenny A Greig, Qiang Wang, Amanda L Reicherter, Shu-Jen Chen, Alexandra L Hanlon, Christopher H Tipper, K Reed Clark, Samuel Wadsworth, Lili Wang, James M Wilson
Adeno-associated viral (AAV) vectors are promising vehicles for hemophilia gene therapy, with favorable clinical trial data seen in the treatment of hemophilia B. In an effort to optimize the expression of human coagulation factor VIII (hFVIII) for the treatment of hemophilia A, we performed an extensive study with numerous combinations of liver-specific promoter and enhancer elements with a codon-optimized hFVIII transgene. After generating 42 variants of three reduced-size promoters and three small enhancers, transgene cassettes were packaged within a single AAV capsid, AAVrh10, to eliminate performance differences due to the capsid type...
January 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28052693/safety-and-efficacy-of-ex-vivo-donor-lung-adenoviral-il-10-gene-therapy-in-a-large-animal-lung-transplant-survival-model
#3
Tiago Noguchi Machuca, Marcelo Cypel, Riccardo Bonato, Jonathan C Yeung, Yi-Min Chun, Stephen Juvet, Guan Zehong, David M Hwang, Manyin Chen, Tomohito Saito, Constantine Harmantas, Beverly Davidson, Thomas K Waddell, Mingyao Liu, Shaf Keshavjee
OBJECTIVE: Ex vivo normothermic lung perfusion (EVLP) is a novel platform and method developed to facilitate functional assessment and implementation of advanced therapies for donor lungs prior to transplantation. We aimed to determine the safety and immunological and functional benefits of ex vivo adenoviral human IL-10 (AdhIL-10) gene delivery to prevent the development of primary graft dysfunction in a large animal survival model. METHODS: Pig donor lungs were retrieved, preserved for 6 hours at 4oC and then randomly assigned to 4 groups: 1) AdhIL-10 Gene Therapy: 12 hours EVLP + AdhIL-10 intra-bronchial delivery; 2) EVLP-control: 12 hours EVLP; 3) Vector-control: 12 hours EVLP + adenoviral vector intra-bronchial delivery; and 4) Prolonged hypothermic preservation: Additional 12 hours of cold ischemia...
January 4, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042949/recombinant-parvoviruses-armed-to-deliver-cxcl4l1-and-cxcl10-are-impaired-in-their-antiangiogenic-and-antitumoral-effects-in-a-kaposi-sarcoma-tumor-model-due-to-the-chemokines-interference-with-the-virus-cycle
#4
Christiane Dinsart, Kalliopi Pervolaraki, Alexandra Stroh-Dege, Muriel Lavie, Isabelle Ronsse, Jean Rommelaere, Jo Van Damme, Katrien Van Raemdonck, Sofie Struyf
Application of oncolytic viruses is a valuable option to broaden the armament of anti-cancer therapies as these combine specific cytotoxic effects and immune-stimulating properties. The self-replicating H-1 parvovirus (H-1PV) is a prototypical oncolytic virus that besides targeting tumor cells also infects endothelial cells, thus combining oncolytic and angiostatic traits. To increase its therapeutic value, H-1PV can be armed with cytokines or chemokines to enhance the immunological response. Some chemokines, more specifically the CXCR3 ligands CXCL4L1 and CXCL10 combine immune-stimulating properties with angiostatic activity...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042948/bacmam-delivery-of-a-protective-gene-to-reduce-renal-ischemia-reperfusion-injury
#5
Elisabetta Hitchman, Richard Brian Hitchman, Linda A King
Ischaemia-reperfusion (I/R) injury remains the primary contributor to delayed graft function in kidney transplantation. The beneficial application of manganese superoxide dismutase (sod), delivered by a BacMam vector, against renal I/R injury has not been evaluated previously. Therefore, in this study we overexpressed sod-2 in proximal tubular epithelial (HK-2) cells and porcine kidney organs during simulated renal I/R injury. Incubation of HK-2 cells with antimycin A and 2-deoxyglucose resulted in a significant decrease in intracellular ATP levels; following reperfusion, ATP levels significantly increased overtime in cells overexpressing sod-2...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042947/efficient-transduction-of-human-and-rhesus-macaque-primary-t-cells-by-a-modified-human-immunodeficiency-virus-type-1-hiv-1-based-lentiviral-vector
#6
Huan He, Jing Xue, Weiming Wang, Lihong Liu, Chaobaihui Ye, Zhe Cong, Jason Kimata, Chuan Qin, Paul Zhou
HIV-1-based lentiviral vectors efficiently transduce genes to human, but not rhesus, primary T cells and hematopoietic stem cells (HSCs). The poor transduction of HIV-1 vectors to rhesus cells is mainly due to species-specific restriction factors such as rhesus TRIM5α. Previously, several strategies to modify HIV-1 vectors were developed to overcome rhesus TRIM5α restriction. While the modified HIV-1 vectors efficiently transduce rhesus HSCs, they remain suboptimal for rhesus primary T cells. Recently, HIV-1 variants that encode combinations of LNEIE mutations in capsid (CA) protein and SIVmac239 Vif were found to replicate efficiently in rhesus primary T cells...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042945/minicircle-orip-mir-31-as-a-novel-ebna1-specific-mirna-therapy-approach-for-nasopharyngeal-carcinoma
#7
Jiang-Xue Wu, Xin Tan, Jiaxin Lin, Luping Yuan, Jiemin Chen, Lin Qiu, Wen-Lin Huang
MicroRNAs (miRNAs) are important post-transcriptional regulators that control cancer development and progression. However, the application of miRNA therapy in cancer has been hampered by a lack of an efficient and targeted delivery system. In our previous studies, an oriP promoter-based minicircle system successfully mediated targeted foreign gene expression in EBNA1-positive nasopharyngeal carcinoma (NPC). However, it remains to be evaluated whether this system can be applied for tumor miRNA therapy. miR-31-5p, a tumor suppressive miRNA involved in the tumorigenesis of EBV-positive NPC, was selected as the therapeutic miRNA to be transferred...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042944/comparison-of-serum-raav-serotype-specific-antibodies-in-patients-with-duchenne-muscular-dystrophy-becker-muscular-dystrophy-inclusion-body-myositis-or-gne-myopathy
#8
Deborah Zygmunt, Kelly E Crowe, Kevin Flanigan, Paul T Martin
Recombinant Adeno-associated virus (rAAV) is a commonly used gene therapy vector for the delivery of therapeutic transgenes in a variety of human diseases, but pre-existing serum antibodies to viral capsid proteins can greatly inhibit rAAV transduction of tissues. We have assayed serum from patients with Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (DMD), Inclusion Body Myositis (IBM), and GNE myopathy (GNE). These were compared to serum from otherwise normal human subjects to determine the extent of pre-existing serum antibodies to rAAVrh74, rAAV1, rAAV2, rAAV6, rAAV8 and rAAV9...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042943/the-impact-of-aav-capsid-specific-t-cell-responses-on-design-and-outcome-of-clinical-gene-transfer-trials-with-recombinant-aav-vectors-an-evolving-controversy
#9
Hildegund Cj Ertl, Katherine A High
Recombinant adenovirus-associated (rAAV) vectors due to their ease of construction, wide tissue tropism and lack of pathogenicity remain at the forefront for long-term gene replacement therapy. In spite of very encouraging pre-clinical results, clinical trials were initially unsuccessful; expression of the rAAV vector-delivered therapeutic protein was transient. Loss of expression was linked to an expansion of AAV capsid-specific T cell responses, leading to the hypothesis that rAAV vectors recall pre-existing memory T cells that had been induced by natural infections with AAV together with a helper virus...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/27967241/acute-myeloid-leukemia-targeting-by-chimeric-antigen-receptor-t-cells-bridging-the-gap-from-preclinical-modeling-to-human-studies
#10
Maria Caterina Rotiroti, Silvia Arcangeli, Monica Casucci, Vincenzo Perriello, Attilio Bondanza, Andrea Biondi, Sarah Tettamanti, Ettore Biagi
Acute myeloid leukemia (AML) still represents an unmet clinical need for adult and pediatric high-risk patients, thus demanding advanced and personalized therapies. In this regard, different targeted immunotherapeutic approaches are available, ranging from naked monoclonal antibodies (mAb) to conjugated and multifunctional mAbs (i.e., BiTEs and DARTs). Recently, researchers have focused their attention on novel techniques of genetic manipulation specifically to redirect cytotoxic T cells endowed with chimeric antigen receptors (CARs) toward selected tumor associated antigens...
December 1, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27889981/chimeric-trojan-protein-insertion-in-lentiviral-membranes-makes-lentiviruses-susceptible-to-neutralization-by-anti-tetanus-serum-antibodies
#11
Anita Le Heron, Steven Patterson, Rafael J Yáñez-Muñoz, George Dickson
This study describes the initial testing of a novel strategy for neutralization of lentiviruses using the fundamental biology of enveloped viruses' assembly and budding. In the field of gene therapy, viral vector surface proteins have been manipulated in order to redirect host cell specificity by alteration of pseudo-types. This study tested whether known viral pseudo-typing proteins or surface proteins known to be recruited to the human immunodeficiency virus (HIV) envelope could be engineered to carry neutralizing epitopes from another microorganism onto the lentiviral surface...
November 26, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27842439/stable-in-vivo-transgene-expression-in-endothelial-cells-with-helper-dependent-adenovirus-roles-of-promoter-and-interleukin-10
#12
Nagadhara Dronadula, Bradley K Wacker, Reginald Van Der Kwast, Jingwan Zhang, David A Dichek
Our long-term goal is to prevent or reverse atherosclerosis by delivering gene therapy from stably transduced endothelial cells (EC). We previously reported that EC-directed gene therapy with a helper-dependent adenovirus (HDAd) expressing apolipoprotein A-I (apo A-I) retarded development of atherosclerosis in rabbit carotid arteries over a 1-month interval. However, a 70% decline in apo A-I expression during this time raised concerns about long-term efficacy of this approach. Here we report use of several approaches aimed either at preventing this decline or at increasing apo A-I expression from HDAd at all time points: codon optimization, deletion of 3' untranslated sequences, substitution of a synthetic mammalian-based promoter (4XETE) for the cytomegalovirus (CMV) promoter, and co-transduction with an HDAd expressing interleukin-10...
November 14, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27832705/aav-infection-protection-from-cancer
#13
Arun Srivastava, Barrie Carter
In late 2015, Nault et al1, reported that of 193 patients with hepatocellular carcinoma (HCC), 11 (<6%) contained an integrated genome sequence of the wild type (wt) adeno-associated virus 2 (AAV2), and suggested that AAV2 is associated with oncogenic insertional mutagenesis in human HCC. Although this conclusion was questioned by us2 and others3, in more recent publications, Nault et al4-7, continue to insist that AAV2 is an oncogenic virus in initiating HCC. Interestingly, Park et al8 recently reported that following evaluation of a total of 289 unrelated patients with HCC, the presence of AAV2 DNA was detected in tumor tissues from only 2 patients (<1%), and concluded that AAV2-mediated HCC is very rare in Korean patients...
November 10, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27832700/systemic-correction-of-murine-glycogen-storage-disease-type-iv-by-an-aav-mediated-gene-therapy
#14
Haiqing Yi, Quan Zhang, Elizabeth D Brooks, Chunyu Yang, Beth L Thurberg, Priya S Kishnani, Baodong Sun
Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (AAV) vector in a mouse model of adult form of GSD IV (Gbe1(ys/ys)). An AAV serotype 9 (AAV9) vector containing a human GBE expression cassette (AAV-GBE) was intravenously injected into 14-day-old Gbe1(ys/ys) mice at a dose of 5 × 10(11) vector genomes per mouse...
November 10, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27806643/manganese-superoxide-dismutase-gene-modified-mesenchymal-stem-cells-attenuates-acute-radiation-induced-lung-injury
#15
HaiXu Chen, Hang Xiang, BenYan Wu, XiaoMei Zhang, Ming Li, Juan Liu, Jun Li, ZhaoQi Ren, Bin Du, KunLun He, Qiang Zeng, Chao Yang
Radiation-induced lung injury (RILI) is a major clinical complication for radiotherapy in thoracic tumors. An immediate effect of lung irradiation is the generation of reactive oxygen (ROS) that can produce oxidative damage to DNA, lipids, and proteins resulting in lung cell injury or death. Currently, the medical management of RILI remains supportive. Therefore, there is an urgent need for the development of countermeasures. The present study was aimed to evaluate the protective effect of manganese superoxide dismutase (MnSOD) gene modified mesenchymal stem cells (MSCs) to facilitate the improved recovery of RILI...
November 2, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27806641/empty-capsids-and-macrophage-inhibition-depletion-increase-raav-transgene-expression-in-joints-of-both-healthy-and-arthritic-mice
#16
Caroline J Aalbers, Niels Broekstra, Mariska van Geldorp, Emiel Kramer, Sofia Ramiro, Paul P Tak, Margriet J Vervoordeldonk, Jonathan D Finn
Gene therapy has potential to treat rheumatic diseases; however, the presence of macrophages in the joint might hamper adeno-associated viral vector-mediated gene delivery. Here we demonstrate that in arthritic, but also in healthy, mice administration of agents that influence macrophage activity/number and/or addition of empty decoy capsids substantially improve the efficacy of recombinant adeno-associated viral vector 5 transgene expression in the joint. Pretreatment with triamcinolone or clodronate liposomes improved luciferase expression over a period of 4 weeks...
November 2, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27802782/treatment-of-human-b-cell-lymphomas-using-minicircle-dna-vector-expressing-anti-cd3-cd20-in-a-mouse-model
#17
Xiaojuan Pang, Fei Ma, Peifa Zhang, Yujian Zhong, Jing Zhang, Tianyan Wang, Gang Zheng, Xiaohu Hou, Jing Zhao, Chengyi He, Zhi-Ying Chen
Bispecific antibodies (BsAbs), capable of directing T cells to kill specific cancer cells by transiently binding the two cell types, have emerged as one class of promising cancer immunotherapies. However, their wide clinical application might be hampered by two deficiencies: high cost and inconvenience in drug administration. This study presents concept-proving data that these problems could be bypassed by using an enhanced nonviral DNA vector minicircle (MC) to produce BsAb in vivo. It was found that the anti-CD3/CD20 produced from the minicircle (MC...
November 1, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27802778/transplantation-of-adipose-tissue-derived-mesenchymal-stem-cell-atmsc-expressing-alpha-1-antitrypsin-reduces-bone-loss-in-ovariectomized-osteoporosis-mice
#18
Mohammad Ahsanul Akbar, Yuanqing Lu, Ahmed S Elshikha, Mong-Jen Chen, Ye Yuan, Elizabeth M Whitley, L Shannon Holliday, Lung-Ji Chang, Sihong Song
Osteoporosis is a common health problem severely affecting the quality of life of many people, especially women. Current treatment options for osteoporosis are limited due to their association with several side-effects and moderate efficacy. Therefore, novel therapies for osteoporosis are needed. This study tested the feasibility of adipose tissue-derived mesenchymal stem cell (ATMSC)-based human alpha-1 antitrypsin (hAAT, SERPINA1) gene therapy for the prevention of bone loss in an ovariectomized (OVX) mouse model...
November 1, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/28026991/correction-to-hum-gene-ther-2016-27-10-749-757
#19
(no author information available yet)
No abstract text is available yet for this article.
January 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/27927014/genetic-modification-of-the-lung-directed-toward-treatment-of-human-disease
#20
Dolan Sondhi, Katie M Stiles, Bishnu P De, Ronald G Crystal
Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy, and lung cancer, infections such as respiratory syncytial virus (RSV) and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection, and lung injury...
January 2017: Human Gene Therapy
journal
journal
30464
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"