scholarly journals Sterile Abscess in the Myocardium after Direct Intramyocardial Injection Related to Gene Therapy in a Swine Model

2011 ◽  
Vol 2011 ◽  
pp. 1-2 ◽  
Author(s):  
Kiyotake Ishikawa ◽  
Dennis Ladage ◽  
Lisa Tilemann ◽  
Yoshiaki Kawase ◽  
Roger J. Hajjar
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Viral Vectors ◽  
Swine Model ◽  
Clinical Settings ◽  
Intramyocardial Injection ◽  
New Therapy ◽  
Sterile Abscess ◽  
Efficient Gene ◽  
Cardiac Gene

Cardiac gene therapy is one of the most promising approaches to cure patients with cardiac dysfunctions. Many ways of efficient gene transfer using viral vectors are tested, and some of them are already used in clinical settings. However, it is always important to be keenly alert to the possible complications when a new therapy is introduced. We present a case of myocardial sterile abscess in a swine model associated with a direct myocardial injection.

scholarly journals Gene Therapy: The Molecular Bandage for Treating Genetic Disorders

1970 ◽  
Vol 3 (1) ◽  
pp. 24-27
Author(s):  
Md Manjurul Karim
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Genetic Disorders ◽  
Clinical Status ◽  
Genetic Material ◽  
Review Article ◽  
Cell Tissue ◽  
Efficient Gene ◽  
Effective Delivery ◽  
A Cell

The concept of gene therapy involves the transfer of genetic material into a cell, tissue, or whole organ, with a view to curing a disease or at least improving the clinical status of a patient. Much of its success relies heavily on the development of an effective delivery system that is capable of efficient gene transfer in a variety of tissues, without causing any associated pathogenic effects. Viral vectors currently offer the best choice for efficient gene delivery, what has been discussed in this review article. Their performance and pathogenecity has been evaluated in animal models, and encouraging results form the basis for clinical trials to treat genetic disorders and acquired diseases. Despite some initial success in these trials, vector development remains a seminal concern for improved gene therapy technologies. DOI: http://dx.doi.org/10.3329/akmmcj.v3i1.10110 AKMMCJ 2012; 3(1): 24-27

Adeno-Associated Viral Vectors for Gene Transfer and Gene Therapy

1999 ◽  
Vol 380 (6) ◽  
Author(s):  
H. Büeler
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Delivery Systems ◽  
Adeno Associated Virus ◽  
Viral Genes ◽  
Virus Recombinant

AbstractAdeno-associated virus (AAV) is a defective, non-pathogenic human parvovirus that depends for growth on coinfection with a helper adenovirus or herpes virus. Recombinant adeno-associated viruses (rAAVs) have attracted considerable interest as vectors for gene therapy. In contrast to other gene delivery systems, rAAVs lack all viral genes and show long-term gene expression

scholarly journals Evaluation of AAV-DJ vector for retinal gene therapy

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6317 ◽  
Author(s):  
Yusaku Katada ◽  
Kenta Kobayashi ◽  
Kazuo Tsubota ◽  
Toshihide Kurihara
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Cell Types ◽  
Egfp Expression ◽  
Adeno Associated Virus ◽  
Photoreceptor Layer ◽  
Mueller Cells ◽  
Efficient Gene ◽  
Clinical Gene Therapy ◽  
Preclinical And Clinical Studies

Purpose The most common virus vector used in gene therapy research for ophthalmologic diseases is the adeno-associated virus (AAV) vector, which has been used successfully in a number of preclinical and clinical studies. It is important to evaluate novel AAV vectors in animal models for application of clinical gene therapy. The AAV-DJ (type 2/type 8/type 9 chimera) was engineered from shuffling eight different wild-type native viruses. In this study, we investigated the efficiency of gene transfer by AAV-DJ injections into the retina. Methods One microliter of AAV-2-CAGGS-EGFP or AAV-DJ-CAGGS-EGFP vector at a titer of 1.4 × 10e12 vg/ml was injected intravitreally or subretinally in each eye of C57BL/6 mice. We evaluated the transduction characteristics of AAV-2 and -DJ vectors using fluorescence microscopy and electroretinography. Results The results confirmed that AAV-DJ could deeply transfer gene to photoreceptor layer with intravitreal injection and has an efficient gene transfer to various cell types especially the Mueller cells in the retina. Retinal function was not affected by AAV-DJ infection or ectopic EGFP expression. Conclusions The AAV-DJ vector efficiently induces the reporter gene in both the inner and outer murine retina without functional toxicity. These data indicated that the AAV-DJ vector is a useful tool for the gene therapy research targeting retinal disorders.

scholarly journals Nonviral Gene Therapy for Cancer: A Review

Diseases ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 57 ◽  
Author(s):  
Chiaki Hidai ◽  
Hisataka Kitano
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Viral Vectors ◽  
Viral Vector ◽  
Transfer Efficiency ◽  
Nonviral Vectors ◽  
Apparent Lack ◽  
Gene Transfer Efficiency ◽  
Relative Safety

Although the development of effective viral vectors put gene therapy on the road to commercialization, nonviral vectors show promise for practical use because of their relative safety and lower cost. A significant barrier to the use of nonviral vectors, however, is that they have not yet proven effective. This apparent lack of interest can be attributed to the problem of the low gene transfer efficiency associated with nonviral vectors. The efficiency of gene transfer via nonviral vectors has been reported to be 1/10th to 1/1000th that of viral vectors. Despite the fact that new gene transfer methods and nonviral vectors have been developed, no significant improvements in gene transfer efficiency have been achieved. Nevertheless, some notable progress has been made. In this review, we discuss studies that report good results using nonviral vectors in vivo in animal models, with a particular focus on studies aimed at in vivo gene therapy to treat cancer, as this disease has attracted the interest of researchers developing nonviral vectors. We describe the conditions in which nonviral vectors work more efficiently for gene therapy and discuss how the goals might differ for nonviral versus viral vector development and use.

Abstract 11987: Adenoviral Intramyocardial VEGF-D Gene Transfer Increases Myocardial Perfusion in Refractory Angina Patients

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Iiro Hassinen ◽  
Juha Hartikainen ◽  
Antti Hedman ◽  
Antti Kivelä ◽  
Antti Saraste ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Myocardial Perfusion ◽  
Left Ventricle ◽  
Control Group ◽  
Transseptal Puncture ◽  
Refractory Angina ◽  
Intramyocardial Injection ◽  
Perfusion Reserve ◽  
Flow Reserve

Background: There is a rapidly growing number of refractory angina patients who in spite of the optimal medical therapy are severely symptomatic and who are not suitable for revascularization. Proangiogenic gene therapy is a potential new treatment for these patients. We evaluated for the first time safety, feasibility and efficacy of adenoviral (Ad) gene therapy using a new member of the VEGF family, VEGF-D, in the treatment of refractory angina. Methods and Results: KAT301 trial is a randomized, placebo-controlled, single-blinded phase I/II study. A total of 30 patients were randomized to intramyocardial AdVEGF-D gene transfer (VEGF group) or placebo (control group) with a 4:1 ratio. VEGF group underwent transseptal puncture and electroanatomical mapping of left ventricle with NOGA system (Cordis Corp), followed by intramyocardial injection of AdVEFG-D in the ischemic areas. The control group underwent transseptal puncture, left ventricle mapping and intracardiac saline infusion. Vital signs and laboratory assessments were measured at baseline and at 1, 2, 7,14 days and 3 months after the gene therapy to evaluate the safety and feasibility. Twenty patients underwent assessment of myocardial perfusion and blood flow reserve at rest and during adenosine induced exercise with positron emission tomography (15O-PET) at baseline and three months after the procedure. Mild transient elevation in body temperature and CRP and moderate hypotension was detected in VEGF group after the procedure. Troponine-T was elevated in both groups after the procedure but was normalized in two days. Perfusion reserve at 3 months in the myocardial segment with the lowest perfusion reserve at baseline increased significantly in the VEGF group (0.93±0.30 to 1.21±0.39, p=0.035) but not in the controls (1.21±0.63 to 1.53±0.67, p=0.343). No antibody responses were found against the transgene in the VEGF group after the treatment. Conclusion: Intramyocardial AdVEGF-D gene therapy is well tolerated in refractory angina patients. Changes in PET analysis at 3 months indicate that gene therapy can enhance myocardial perfusion in segments with the lowest perfusion reserve. Based on the results a randomized, controlled, blinded phase II/III trial is justified.

Advanced Materials for Gene Delivery

2014 ◽  
Vol 995 ◽  
pp. 29-47 ◽  
Author(s):  
Mohammad A. Jafar Mazumder ◽  
Md. Hasan Zahir ◽  
Sharif F. Zaman
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Genetic Disorders ◽  
Basic Research ◽  
Advanced Materials ◽  
Clinical Settings ◽  
Efficient Gene ◽  
Efficient Delivery ◽  
Promising Treatment

Gene therapy is a widespread and promising treatment of many diseases resulting from genetic disorders, infections and cancer. The feasibility of the gene therapy is mainly depends on the development of appropriate method and suitable vectors. For an efficient gene delivery, it is very important to use a carrier that is easy to produce, stable, non-oncogenic and non-immunogenic. Currently most of the vectors actually suffer from many problems. Therefore, the ideal gene therapy delivery system should be developed that can be easily used for highly efficient delivery and able to maintain long-term gene expression, and can be applicable to basic research as well as clinical settings. This article provides a brief over view on the concept and aim of gene delivery, the different gene delivery systems and use of different materials as a carrier in the area of gene therapy.

Gene Transfer Using Nonviral Delivery Systems

2006 ◽  
Vol 26 (6) ◽  
pp. 633-640 ◽  
Author(s):  
Masanobu Miyazaki ◽  
Yoko Obata ◽  
Katsushige Abe ◽  
Akira Furusu ◽  
Takehiko Koji ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Peritoneal Dialysis ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Delivery System ◽  
Viral Vectors ◽  
Nonviral Vectors ◽  
Gene Delivery System ◽  
Peritoneal Membrane ◽  
Peritoneal Function

In peritoneal dialysis, loss of peritoneal function is a major factor in treatment failure. The alterations in peritoneal function are related to structural changes in the peritoneal membrane, including peritoneal sclerosis with increased extracellular matrix. Although peritoneal sclerosis is considered reversible to some extent through peritoneal rest, which improves peritoneal function and facilitates morphological changes, there has been no therapeutic intervention and no drug against the development and progression of peritoneal sclerosis. Using recent biotechnological advances in genetic engineering, a strategy based on genetic modification of the peritoneal membrane could be a potential therapeutic maneuver against peritoneal sclerosis and peritoneal membrane failure. Before this gene therapy may be applied clinically, a safe and effective gene delivery system as well as the selection of a gene therapy method must be established. There are presently two kinds of gene transfer vectors: viral and nonviral. Viral vectors are used mainly as a gene delivery system in the field of continuous ambulatory peritoneal dialysis research; however, they have several problems such as immunogenicity and toxicity. On the other hand, nonviral vectors have several advantages over viral vectors. We review here gene transfer using nonviral vector systems in the peritoneum: electroporation, liposomes, and cationized gelatin microspheres. In the field of peritoneal dialysis, gene therapy research using nonviral vectors is presently limited. Improvement in delivery methods together with an intelligent design of targeted genes has brought about large degrees of enhancement in the efficiency, specificity, and temporal control of nonviral vectors.

IL-7 surface-engineered lentiviral vectors promote survival and efficient gene transfer in resting primary T lymphocytes

Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2167-2174 ◽  
Author(s):  
Els Verhoeyen ◽  
Valerie Dardalhon ◽  
Odile Ducrey-Rundquist ◽  
Didier Trono ◽  
Naomi Taylor ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
T Cell ◽  
Gene Transfer ◽  
Lentiviral Vectors ◽  
Target Cells ◽  
Interleukin 7 ◽  
Efficient Gene ◽  
Cognate Antigen ◽  
Therapy Target

Important gene therapy target cells such as resting human T cells are refractory to transduction with lentiviral vectors. Completion of reverse transcription, nuclear import, and subsequent integration of the lentiviral genome occur in these cells only if they have been activated. In T-cell–based gene therapy trials performed to date, cells have been activated via their cognate antigen receptor. To couple activation with gene transfer, we previously generated lentiviral vectors displaying an anti-CD3 scFv fragment that allowed up to 48% transduction of freshly isolated T cells. However, transduction of highly purified resting T cells with these anti-CD3–displaying lentiviral vectors was inefficient and shifted the T cells from the naive to the memory phenotype. Here, we describe interleukin-7 (IL-7)–displaying HIV-1–derived vectors. Like recombinant IL-7, these modified particles could promote the survival of primary T cells placed in culture without inducing a naive-to-memory phenotypic switch. Furthermore, a single exposure to the IL-7–displaying vectors resulted in efficient gene transfer in both resting memory adult T cells and naive cord blood T cells. With adult naive T cells, preactivation with recombinant IL-7 was necessary for efficient gene transfer. Altogether, these results suggest that IL-7–displaying vectors could constitute interesting tools for T-cell–targeted gene therapy.

Stable transduction of quiescent T cells without induction of cycle progression by a novel lentiviral vector pseudotyped with measles virus glycoproteins

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 4843-4852 ◽  
Author(s):  
Cecilia Frecha ◽  
Caroline Costa ◽  
Didier Nègre ◽  
Emmanuel Gauthier ◽  
Stephen J. Russell ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Therapy ◽  
T Cells ◽  
T Cell ◽  
Gene Transfer ◽  
Measles Virus ◽  
Lentiviral Vectors ◽  
Cell Cycle Entry ◽  
Efficient Gene ◽  
Quiescent T Cells

AbstractA major limitation of current lentiviral vectors (LVs) is their inability to govern efficient gene transfer into quiescent cells such as primary T cells, which hampers their application for gene therapy. Here we generated high-titer LVs incorporating Edmonston measles virus (MV) glycoproteins H and F on their surface. They allowed efficient transduction through the MV receptors, SLAM and CD46, both present on blood T cells. Indeed, these H/F-displaying vectors outperformed by far VSV-G-LVs for the transduction of IL-7–prestimulated T cells. More importantly, a single exposure to these H/F-LVs allowed efficient gene transfer in quiescent T cells, which are not permissive for VSV-G-LVs that need cell-cycle entry into the G1b phase for efficient transduction. High-level transduction of resting memory (50%) and naive (11%) T cells with H/F-LVs, which seemed to occur mainly through SLAM, was not at cost of cell-cycle entry or of target T-cell activation. Finally, the naive or memory phenotypes of transduced resting T cells were maintained and no changes in cytokine profiles were detected, suggesting that T-cell populations were not skewed. Thus, H/F-LV transduction of resting T cells overcomes the limitation of current lentiviral vectors and may improve the efficacy of T cell–based gene therapy.

Sign in / Sign up

Export Citation Format

Share Document