scholarly journals Gene Delivery Technologies for Efficient Genome Editing: Applications in Gene Therapy

10.5772/62776 ◽  
2016 ◽  
Author(s):  
Francisco Martin ◽  
Sabina Sánchez-Hernández ◽  
Alejandra Gutierrez-Guerrero ◽  
Karim Benabdellah
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Genome Editing

scholarly journals Gene Therapy to the Retina and the Cochlea

2021 ◽  
Vol 15 ◽  
Author(s):  
Ryan Crane ◽  
Shannon M. Conley ◽  
Muayyad R. Al-Ubaidi ◽  
Muna I. Naash
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Gene Delivery ◽  
Genome Editing ◽  
Retinal Diseases ◽  
Preclinical Development ◽  
Hearing Disorders ◽  
Gene Therapies ◽  
Current State ◽  
Sensory Disorders

Vision and hearing disorders comprise the most common sensory disorders found in people. Many forms of vision and hearing loss are inherited and current treatments only provide patients with temporary or partial relief. As a result, developing genetic therapies for any of the several hundred known causative genes underlying inherited retinal and cochlear disorders has been of great interest. Recent exciting advances in gene therapy have shown promise for the clinical treatment of inherited retinal diseases, and while clinical gene therapies for cochlear disease are not yet available, research in the last several years has resulted in significant advancement in preclinical development for gene delivery to the cochlea. Furthermore, the development of somatic targeted genome editing using CRISPR/Cas9 has brought new possibilities for the treatment of dominant or gain-of-function disease. Here we discuss the current state of gene therapy for inherited diseases of the retina and cochlea with an eye toward areas that still need additional development.

Exosome as a Natural Gene Delivery Vector for Cancer Treatment

2020 ◽  
Vol 20 (11) ◽  
pp. 821-830
Author(s):  
Prasad Pofali ◽  
Adrita Mondal ◽  
Vaishali Londhe
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Nucleic Acids ◽  
Cancer Treatment ◽  
Intestinal Barrier ◽  
Gene Carrier ◽  
Gene Delivery Vector ◽  
Delivery Vector

Background: Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular environment by most of the cell types in-vivo and in-vitro. As a natural nanocarrier, exosomes are immunologically inert, biocompatible, and can cross biological barriers like the blood-brain barrier, intestinal barrier, and placental barrier. Objective: This review focusses on the role of exosome as a carrier to efficiently deliver a gene for cancer treatment and diagnosis. The methods for loading of nucleic acids onto the exosomes, advantages of exosomes as a smart intercellular shuttle for gene delivery and therapeutic applications as a gene delivery vector for siRNA, miRNA and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and also the limitations of exosomes as a gene carrier are all reviewed in this article. Methods: Mostly, electroporation and chemical transfection are used to prepare gene loaded exosomes. Results: Exosome-mediated delivery is highly promising and advantageous in comparison to the current delivery methods for systemic gene therapy. Targeted exosomes, loaded with therapeutic nucleic acids, can efficiently promote the reduction of tumor proliferation without any adverse effects. Conclusion: In the near future, exosomes can become an efficient gene carrier for delivery and a biomarker for the diagnosis and treatment of cancer.

An artificial cell system for biocompatible gene delivery in cancer therapy

Nanoscale ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 10189-10195 ◽  
Author(s):  
Xin Zhao ◽  
Dongyang Tang ◽  
Ying Wu ◽  
Shaoqing Chen ◽  
Cheng Wang
Keyword(s):  
Gene Therapy ◽  
Cancer Therapy ◽  
Gene Delivery ◽  
Cancer Cells ◽  
Cell System ◽  
Artificial Cell

The artifical cell system for the gene therapy of cancer might be a promising approach for the reversal of neoplastic progress of cancer cells.

scholarly journals How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

2021 ◽  
Vol 22 (14) ◽  
pp. 7545
Author(s):  
Myriam Sainz-Ramos ◽  
Idoia Gallego ◽  
Ilia Villate-Beitia ◽  
Jon Zarate ◽  
Iván Maldonado ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Practice ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Viral Vector ◽  
Clinical Success ◽  
Genetic Material ◽  
Viral Gene ◽  
Promising Alternative ◽  
Vector Systems

Efficient delivery of genetic material into cells is a critical process to translate gene therapy into clinical practice. In this sense, the increased knowledge acquired during past years in the molecular biology and nanotechnology fields has contributed to the development of different kinds of non-viral vector systems as a promising alternative to virus-based gene delivery counterparts. Consequently, the development of non-viral vectors has gained attention, and nowadays, gene delivery mediated by these systems is considered as the cornerstone of modern gene therapy due to relevant advantages such as low toxicity, poor immunogenicity and high packing capacity. However, despite these relevant advantages, non-viral vectors have been poorly translated into clinical success. This review addresses some critical issues that need to be considered for clinical practice application of non-viral vectors in mainstream medicine, such as efficiency, biocompatibility, long-lasting effect, route of administration, design of experimental condition or commercialization process. In addition, potential strategies for overcoming main hurdles are also addressed. Overall, this review aims to raise awareness among the scientific community and help researchers gain knowledge in the design of safe and efficient non-viral gene delivery systems for clinical applications to progress in the gene therapy field.

scholarly journals Progress in Gene Therapy to Prevent Retinal Ganglion Cell Loss in Glaucoma and Leber’s Hereditary Optic Neuropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Sara E. Ratican ◽  
Andrew Osborne ◽  
Keith R. Martin
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Optic Nerve ◽  
Genome Editing ◽  
Optic Neuropathy ◽  
Single Gene ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Potential Use ◽  
Hereditary Optic Neuropathy

The eye is at the forefront of the application of gene therapy techniques to medicine. In the United States, a gene therapy treatment for Leber’s congenital amaurosis, a rare inherited retinal disease, recently became the first gene therapy to be approved by the FDA for the treatment of disease caused by mutations in a specific gene. Phase III clinical trials of gene therapy for other single-gene defect diseases of the retina and optic nerve are also currently underway. However, for optic nerve diseases not caused by single-gene defects, gene therapy strategies are likely to focus on slowing or preventing neuronal death through the expression of neuroprotective agents. In addition to these strategies, there has also been recent interest in the potential use of precise genome editing techniques to treat ocular disease. This review focuses on recent developments in gene therapy techniques for the treatment of glaucoma and Leber’s hereditary optic neuropathy (LHON). We discuss recent successes in clinical trials for the treatment of LHON using gene supplementation therapy, promising neuroprotective strategies that have been employed in animal models of glaucoma and the potential use of genome editing techniques in treating optic nerve disease.

scholarly journals Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy

2002 ◽  
Vol 9 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Anders Høgset ◽  
Birgit Øvstebø Engesæter ◽  
Lina Prasmickaite ◽  
Kristian Berg ◽  
Øystein Fodstad ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Cancer Gene Therapy ◽  
Specific Gene ◽  
Cancer Gene ◽  
Delivery Technology

Abstract 339: Long-term AAV6-βARKct Myocardial Gene Therapy Improves Cardiac Function Via Restoration Of β-Adrenergic Receptor Signaling And Neurohormonal Status Of The Failing Heart

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Giuseppe Rengo ◽  
Anastasios Lymperopoulos ◽  
Carmela Zincarelli ◽  
Maria Donniacuo ◽  
Stephen Soltys ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Cardiac Function ◽  
Adrenergic Receptor ◽  
Fluorescent Protein ◽  
Heart Function ◽  
Weight Ratio ◽  
Intramyocardial Injection ◽  
Molecular Abnormalities ◽  
Virus Serotype

BACKGROUND: The up-regulation of G protein-coupled receptor kinase-2 (GRK2) that is present in compromised myocardium contributes to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function in heart failure (HF). The peptide βARKct, which inhibits the activation of GRK2, has been shown in acute gene transfer experiments to rescue HF. This study was designed to evaluate chronic βARKct expression in post-myocardial infarction (MI) induced HF using stable myocardial gene delivery with adeno-associated virus serotype-6 (AAV6). METHODS AND RESULTS: In 12 week post-MI HF rats, we delivered βARKct or as a control, Green Fluorescent Protein, via direct intramyocardial injection. We also treated groups with concurrent administration of metoprolol. We found robust and long-lasting (up to 12 weeks post-delivery) transgene expression in the left ventricle (LV) and βARKct expression resulted in significantly improved global heart function as LV ejection fraction and ±dP/dt were increased, whereas LV end diastolic diameter and pressure were decreased. At the molecular level, cardiac βAR density and cAMP accumulation significantly improved over control groups. Fibrotic and hypertrophy markers, as well as heart-to-body weight ratio were markedly decreased by βARKct gene therapy indicating active reversal of adverse LV remodeling. For the first time, we found that chronic βARKct expression and normalization of cardiac βAR signaling led to a reduction of circulating levels of cardiotoxic neurohormones (catecholamines and aldosterone) demonstrating a potential additive mechanism of GRK2 inhibition. Concomitant metoprolol administration preserved the gain in inotropy achieved by βARKct, suggesting compatibility of these two therapeutic modalities, however, metoprolol alone only prevented the deterioration of cardiac function in HF. CONCLUSIONS : Chronic cardiac βARKct gene therapy for HF treatment via AAV6-mediated intracardiac gene delivery is feasible and results in improved cardiac function accompanied by restoration of βAR molecular abnormalities and amelioration of neurohormonal status of HF. These findings suggest βARKct gene therapy might be clinically applicable and of significant value for human HF treatment. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).

Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa

2016 ◽  
Vol 12 (8) ◽  
pp. 2251-2260 ◽  
Author(s):  
Andrea Pensado ◽  
Francisco J. Diaz-Corrales ◽  
Berta De la Cerda ◽  
Lourdes Valdés-Sánchez ◽  
Ana Aramburu del Boz ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Retinitis Pigmentosa ◽  
Viral Vectors
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