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 Immunological Ignorance Allows Long-Term Gene Expression After Perinatal Recombinant Adeno-Associated Virus-Mediated Gene Transfer to Murine Airways

2014 ◽  
Vol 25 (6) ◽  
pp. 517-528 ◽  
Author(s):  
Marianne S. Carlon ◽  
Dragana Vidović ◽  
James Dooley ◽  
Marina Mori da Cunha ◽  
Michael Maris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Transfer ◽  
Adeno Associated Virus

scholarly journals Recent Advances in the Development of Bio-Reducible Polymers for Efficient Cancer Gene Delivery Systems

2019 ◽  
Vol 2 (1) ◽  
pp. 6-13 ◽  
Author(s):  
Kiel Sung Yong ◽  
◽  
Wan Kim Sung ◽  
◽  
◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Ribonucleic Acid ◽  
Viral Vectors ◽  
Delivery Systems ◽  
Host Cells ◽  
Viral Gene ◽  
Cancer Gene ◽  
Inherited Disorders ◽  
Messenger Ribonucleic Acid

Gene therapy is the unique method for the use of genetic materials such as Messenger ribonucleic acid (mRNA), plasmid deoxyribonucleic acid (pDNA), and small interfering ribonucleic acid (siRNA) into specific host-cells for the treatment of inherited disorders in any diseases. The successful way to utilize the gene therapy is to develop the efficient cancer gene delivery systems. In this paper, the successful and efficient gene delivery systems are briefly reviewed on the basis of bio-reducible polymeric systems for cancer therapy. The viral gene delivery systems such as RNA-based viral and DNA-based viral vectors are also discussed. The development of bio-reducible polymer for gene delivery system has briefly discussed for the efficient cancer gene delivery of viral vectors and non-viral vectors.

Inactivation of a GFP retrovirus occurs at multiple levels in long-term repopulating stem cells and their differentiated progeny

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 894-901 ◽  
Author(s):  
Christopher A. Klug ◽  
Samuel Cheshier ◽  
Irving L. Weissman
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Gene Therapy ◽  
Stem Cell ◽  
Viral Vectors ◽  
Fluorescent Protein ◽  
Lymphoid Cells ◽  
Gfp Expression ◽  
Hematopoietic Stem

Abstract Hematopoietic stem cell gene therapy holds promise for the treatment of many hematologic disorders. One major variable that has limited the overall success of gene therapy to date is the lack of sustained gene expression from viral vectors in transduced stem cell populations. To understand the basis for reduced gene expression at a single-cell level, we have used a murine retroviral vector, MFG, that expresses the green fluorescent protein (GFP) to transduce purified populations of long-term self-renewing hematopoietic stem cells (LT-HSC) isolated using the fluorescence-activated cell sorter. Limiting dilution reconstitution of lethally irradiated recipient mice with 100% transduced, GFP+ LT-HSC showed that silencing of gene expression occurred rapidly in most integration events at the LT-HSC level, irrespective of the initial levels of GFP expression. When inactivation occurred at the LT-HSC level, there was no GFP expression in any hematopoietic lineage clonally derived from silenced LT-HSC. Inactivation downstream of LT-HSC that stably expressed GFPin long-term reconstituted animals was restricted primarily to lymphoid cells. These observations suggest at least 2 distinct mechanisms of silencing retrovirally expressed genes in hematopoietic cells.

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.

scholarly journals Inducible long-term gene expression in brain with adeno-associated virus gene transfer

Gene Therapy ◽  
1998 ◽  
Vol 5 (12) ◽  
pp. 1604-1611 ◽  
Author(s):  
RP Haberman ◽  
TJ McCown ◽  
RJ Samulski
Keyword(s):  
Gene Expression ◽  
Gene Transfer ◽  
Adeno Associated Virus ◽  
Virus Gene

Long-Term Inducible Gene Expression in the Eye via Adeno-Associated Virus Gene Transfer in Nonhuman Primates

2005 ◽  
Vol 16 (2) ◽  
pp. 178-186 ◽  
Author(s):  
Corinna Lebherz ◽  
Alberto Auricchio ◽  
Albert M. Maguire ◽  
Victor M. Rivera ◽  
Waixing Tang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Transfer ◽  
Nonhuman Primates ◽  
Inducible Gene Expression ◽  
Adeno Associated Virus ◽  
Virus Gene ◽  
Inducible Gene

scholarly journals Gene delivery to the hypoglossal motor system: preclinical studies and translational potential

Gene Therapy ◽  
2021 ◽  
Author(s):  
Brendan M. Doyle ◽  
Michele L. Singer ◽  
Thomaz Fleury-Curado ◽  
Sabhya Rana ◽  
Ethan S. Benevides ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Motor System ◽  
Viral Vectors ◽  
Muscle Activation ◽  
Neuromuscular Disorders ◽  
Preclinical Studies ◽  
Adeno Associated Virus ◽  
Tongue Muscle ◽  
Reduced Activity

AbstractDysfunction and/or reduced activity in the tongue muscles contributes to conditions such as dysphagia, dysarthria, and sleep disordered breathing. Current treatments are often inadequate, and the tongue is a readily accessible target for therapeutic gene delivery. In this regard, gene therapy specifically targeting the tongue motor system offers two general strategies for treating lingual disorders. First, correcting tongue myofiber and/or hypoglossal (XII) motoneuron pathology in genetic neuromuscular disorders may be readily achieved by intralingual delivery of viral vectors. The retrograde movement of viral vectors such as adeno-associated virus (AAV) enables targeted distribution to XII motoneurons via intralingual viral delivery. Second, conditions with impaired or reduced tongue muscle activation can potentially be treated using viral-driven chemo- or optogenetic approaches to activate or inhibit XII motoneurons and/or tongue myofibers. Further considerations that are highly relevant to lingual gene therapy include (1) the diversity of the motoneurons which control the tongue, (2) the patterns of XII nerve branching, and (3) the complexity of tongue muscle anatomy and biomechanics. Preclinical studies show considerable promise for lingual directed gene therapy in neuromuscular disease, but the potential of such approaches is largely untapped.

Nonviral gene therapy targeting cardiovascular system

2012 ◽  
Vol 303 (6) ◽  
pp. H629-H638 ◽  
Author(s):  
Cheng-Huang Su ◽  
Yih-Jer Wu ◽  
Hsueh-Hsiao Wang ◽  
Hung-I Yeh
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Potential Method ◽  
Therapeutic Angiogenesis ◽  
Advanced Technology ◽  
Target Cells ◽  
Peripheral Tissues

The goal of gene therapy is either to introduce a therapeutic gene into or replace a defective gene in an individual's cells and tissues. Gene therapy has been urged as a potential method to induce therapeutic angiogenesis in ischemic myocardium and peripheral tissues after extensive investigation in recent preclinical and clinical studies. A successful gene therapy mainly relies on the development of the gene delivery vector. Developments in viral and nonviral vector technology including cell-based gene transfer will further improve transgene delivery and expression efficiency. Nonviral approaches as alternative gene delivery vehicles to viral vectors have received significant attention. Recently, a simple and safe approach of gene delivery into target cells using naked DNA has been improved by combining several techniques. Among the physical approaches, ultrasonic microbubble gene delivery, with its high safety profile, low costs, and repeatable applicability, can increase the permeability of cell membrane to macromolecules such as plasmid DNA by its bioeffects and can provide as a feasible tool in gene delivery. On the other hand, among the promising areas for gene therapy in acquired diseases, ischemic cardiovascular diseases have been widely studied. As a result, gene therapy using advanced technology may play an important role in this regard. The aims of this review focus on understanding the cellular and in vivo barriers in gene transfer and provide an overview of currently used chemical vectors and physical tools that are applied in nonviral cardiovascular gene transfer.

Inactivation of a GFP retrovirus occurs at multiple levels in long-term repopulating stem cells and their differentiated progeny

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 894-901 ◽  
Author(s):  
Christopher A. Klug ◽  
Samuel Cheshier ◽  
Irving L. Weissman
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Gene Therapy ◽  
Stem Cell ◽  
Viral Vectors ◽  
Fluorescent Protein ◽  
Lymphoid Cells ◽  
Gfp Expression ◽  
Hematopoietic Stem

Hematopoietic stem cell gene therapy holds promise for the treatment of many hematologic disorders. One major variable that has limited the overall success of gene therapy to date is the lack of sustained gene expression from viral vectors in transduced stem cell populations. To understand the basis for reduced gene expression at a single-cell level, we have used a murine retroviral vector, MFG, that expresses the green fluorescent protein (GFP) to transduce purified populations of long-term self-renewing hematopoietic stem cells (LT-HSC) isolated using the fluorescence-activated cell sorter. Limiting dilution reconstitution of lethally irradiated recipient mice with 100% transduced, GFP+ LT-HSC showed that silencing of gene expression occurred rapidly in most integration events at the LT-HSC level, irrespective of the initial levels of GFP expression. When inactivation occurred at the LT-HSC level, there was no GFP expression in any hematopoietic lineage clonally derived from silenced LT-HSC. Inactivation downstream of LT-HSC that stably expressed GFPin long-term reconstituted animals was restricted primarily to lymphoid cells. These observations suggest at least 2 distinct mechanisms of silencing retrovirally expressed genes in hematopoietic cells.

Sign in / Sign up

Export Citation Format

Share Document