scholarly journals Gene therapy: progress and predictions

2015 ◽  
Vol 282 (1821) ◽  
pp. 20143003 ◽  
Author(s):  
Mary Collins ◽  
Adrian Thrasher
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Viral Vector ◽  
Single Gene ◽  
Marker Gene ◽  
Cost Effective ◽  
Systemic Injection ◽  
Gene Delivery Vectors ◽  
Cost Effective Method

The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of viral vectors. There are also a number of promising gene therapy approaches for cancer and infectious disease. We predict that the next 25 years will see improvements in safety, efficacy and manufacture of gene delivery vectors and introduction of gene-editing technologies to the clinic. Gene delivery may also prove a cost-effective method for the delivery of biological medicines.

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.

Development and Challenges of Nanovectors in Gene Therapy

Nano LIFE ◽  
2014 ◽  
Vol 04 (03) ◽  
pp. 1441007 ◽  
Author(s):  
Yarong Liu ◽  
Jennifer Rohrs ◽  
Pin Wang
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Nonviral Vectors ◽  
Cellular Compartment ◽  
Current State ◽  
Gene Delivery Vectors ◽  
Wide Range

In recent years, hundreds of genes have been linked to a variety of human diseases, and the field of gene therapy has emerged as a way to treat this wide range of diseases. The main goal of gene therapy is to find a gene delivery vehicle that can successfully target diseased cells and deliver therapeutic genes directly to their cellular compartment. The two main types of gene delivery vectors currently being investigated in clinical trials are recombinant viral vectors and synthetic nonviral vectors. Recombinant viral vectors take advantage of the evolutionarily optimized viral mechanisms to deliver genes, but they can be hard to specifically target in vivo and are also associated with serious side effects. Synthetic nonviral vectors are made out of highly biocompatible lipids or polymers, but they are much less efficient at delivering their genetic payload due to the lack of any active delivery mechanism. This mini review will introduce the current state of gene delivery in clinical trials, and discuss the specific challenges associated with each of these vectors. It will also highlight some specific gaps in knowledge that are limiting the advancement of this field and touch on the current areas of research being explored to overcome them.

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

Gene therapy for critical limb ischemia: Per aspera ad astra

2021 ◽  
Vol 21 ◽  
Author(s):  
Vyacheslav Z. Tarantul ◽  
Alexander V. Gavrilenko
Keyword(s):  
Gene Therapy ◽  
Critical Limb Ischemia ◽  
Viral Vectors ◽  
Ex Vivo ◽  
Single Gene ◽  
Public Health Problem ◽  
Limb Ischemia ◽  
Therapeutic Angiogenesis ◽  
Effective Treatment Option

: Peripheral artery diseases remain a serious public health problem. Although there are many traditional methods for their treatment using conservative therapeutic techniques and surgery, gene therapy is an alternative and potentially more effective treatment option especially for “no option” patients. This review treats the results of many years of research and application of gene therapy as an example of treatment of patients with critical limb ischemia. Data on successful and unsuccessful attempts to use this technology for treating this disease are presented. Trends in changing the paradigm of approaches to therapeutic angiogenesis are noted: from viral vectors to non-viral vectors, from gene transfer to the whole organism to targeted transfer to cells and tissues, from single gene use to combination of genes; from DNA therapy to RNA therapy, from in vivo therapy to ex vivo therapy.

scholarly journals Layered Double Hydroxide as a Potent Non-viral Vector for Nucleic Acid Delivery Using Gene-Activated Scaffolds for Tissue Regeneration Applications

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1219
Author(s):  
Lara S. Costard ◽  
Domhnall C. Kelly ◽  
Rachael N. Power ◽  
Christopher Hobbs ◽  
Sonia Jaskaniec ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Layered Double Hydroxide ◽  
Viral Vectors ◽  
Viral Vector ◽  
Nucleic Acid Delivery ◽  
Safe Alternative ◽  
Transfection Efficacy ◽  
Mass Ratios ◽  
Low Cytotoxicity ◽  
Double Hydroxide

Nonviral vectors offer a safe alternative to viral vectors for gene therapy applications, albeit typically exhibiting lower transfection efficiencies. As a result, there remains a significant need for the development of a nonviral delivery system with low cytotoxicity and high transfection efficacy as a tool for safe and transient gene delivery. This study assesses MgAl-NO3 layered double hydroxide (LDH) as a nonviral vector to deliver nucleic acids (pDNA, miRNA and siRNA) to mesenchymal stromal cells (MSCs) in 2D culture and using a 3D tissue engineering scaffold approach. Nanoparticles were formulated by complexing LDH with pDNA, microRNA (miRNA) mimics and inhibitors, and siRNA at varying mass ratios of LDH:nucleic acid. In 2D monolayer, pDNA delivery demonstrated significant cytotoxicity issues, and low cellular transfection was deemed to be a result of the poor physicochemical properties of the LDH–pDNA nanoparticles. However, the lower mass ratios required to successfully complex with miRNA and siRNA cargo allowed for efficient delivery to MSCs. Furthermore, incorporation of LDH–miRNA nanoparticles into collagen-nanohydroxyapatite scaffolds resulted in successful overexpression of miRNA in MSCs, demonstrating the development of an efficacious miRNA delivery platform for gene therapy applications in regenerative medicine.

scholarly journals Current Status and Challenges Associated with CNS-Targeted Gene Delivery across the BBB

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1216
Author(s):  
Seigo Kimura ◽  
Hideyoshi Harashima
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Neurological Disorders ◽  
Viral Vectors ◽  
New Drugs ◽  
Brain Targeting ◽  
Current Status ◽  
Great Promise ◽  
Targeted Gene Delivery ◽  
The Central Nervous System

The era of the aging society has arrived, and this is accompanied by an increase in the absolute numbers of patients with neurological disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such neurological disorders are serious costly diseases that have a significant impact on society, both globally and socially. Gene therapy has great promise for the treatment of neurological disorders, but only a few gene therapy drugs are currently available. Delivery to the brain is the biggest hurdle in developing new drugs for the central nervous system (CNS) diseases and this is especially true in the case of gene delivery. Nanotechnologies such as viral and non-viral vectors allow efficient brain-targeted gene delivery systems to be created. The purpose of this review is to provide a comprehensive review of the current status of the development of successful drug delivery to the CNS for the treatment of CNS-related disorders especially by gene therapy. We mainly address three aspects of this situation: (1) blood-brain barrier (BBB) functions; (2) adeno-associated viral (AAV) vectors, currently the most advanced gene delivery vector; (3) non-viral brain targeting by non-invasive methods.

Bioreducible, hydrolytically degradable and targeting polymers for gene delivery

2017 ◽  
Vol 5 (18) ◽  
pp. 3253-3276 ◽  
Author(s):  
Ihsan Ullah ◽  
Khan Muhammad ◽  
Mary Akpanyung ◽  
Abdelilah Nejjari ◽  
Agnaldo Luis Neve ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Synthetic Gene ◽  
Suitable Alternative ◽  
Gene Carriers ◽  
Promising Application

Recently, synthetic gene carriers have been intensively developed owing to their promising application in gene therapy and considered as a suitable alternative to viral vectors because of several benefits.

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

Nanotechnology for Gene Delivery to the Eye

2009 ◽  
Vol 03 (01) ◽  
pp. 7 ◽  
Author(s):  
Swita R Singh ◽  
Uday B Kompella ◽  
◽  
Keyword(s):  
Gene Delivery ◽  
Enzymatic Degradation ◽  
Viral Vectors ◽  
Viral Vector ◽  
Target Cells ◽  
Loading Capacity ◽  
Adeno Associated Virus ◽  
Complementary Dna ◽  
Privileged Status ◽  
Potential Applications

The relatively immune-privileged status of the eye makes it an interesting target for gene delivery. Gene delivery to the eye using viral vectors via subretinal and intravitreal injections has been extensively investigated. Recently, the safety of recombinant adeno-associated virus vector expressing RPE65 complementary DNA (cDNA) in a limited clinical trial of three patients has also been reported. Nanotechnology-based non-viral vectors offer the advantages of safety and flexibility in terms of loading capacity and delivery system design compared with viral vectors. An ideal non-viral vector should be non-toxic, efficiently taken up into the target cells and conducive to gene expression, and should protect the gene against enzymatic degradation. Multiple kinds of nanotechnology-based non-viral vectors have been investigated for potential applications for gene delivery to the eye, namely nanoplexes, dendrimers, micelles, nanoparticles and liposomes. This article summarises and discusses key advances in the application of nanotechnology for gene delivery to the eye.

Gene therapy for neurodegenerative and ocular diseases using lentiviral vectors

2005 ◽  
Vol 110 (1) ◽  
pp. 37-46 ◽  
Author(s):  
G. Scott Ralph ◽  
Katie Binley ◽  
Liang-Fong Wong ◽  
Mimoun Azzouz ◽  
Nicholas D. Mazarakis
Keyword(s):  
Gene Therapy ◽  
Nervous System ◽  
Viral Vectors ◽  
Viral Vector ◽  
Lentiviral Vectors ◽  
Great Promise ◽  
Ocular Diseases ◽  
Vector Systems ◽  
Gene Therapy Application ◽  
Wide Range

Gene therapy holds great promise for the treatment of a wide range of inherited and acquired disorders. The development of viral vector systems to mediate safe and long-lasting expression of therapeutic transgenes in specific target cell populations is continually advancing. Gene therapy for the nervous system is particularly challenging due to the post-mitotic nature of neuronal cells and the restricted accessibility of the brain itself. Viral vectors based on lentiviruses provide particularly attractive vehicles for delivery of therapeutic genes to treat neurological and ocular diseases, since they efficiently transduce non-dividing cells and mediate sustained transgene expression. Furthermore, novel routes of vector delivery to the nervous system have recently been elucidated and these have increased further the scope of lentiviruses for gene therapy application. Several studies have demonstrated convincing therapeutic efficacy of lentiviral-based gene therapies in animal models of severe neurological disorders and the push for progressing such vectors to the clinic is ongoing. This review describes the key features of lentiviral vectors that make them such useful tools for gene therapy to the nervous system and outlines the major breakthroughs in the potential use of such vectors for treating neurodegenerative and ocular diseases.

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