scholarly journals Gene Therapy: Design and Prospects for Craniofacial Regeneration

2009 ◽  
Vol 88 (7) ◽  
pp. 585-596 ◽  
Author(s):  
E.L. Scheller ◽  
P.H. Krebsbach
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Genetic Material ◽  
Building Blocks ◽  
Tissue Growth ◽  
Viral Gene ◽  
Insert Size ◽  
Relative Safety ◽  
Size Limitation

Gene therapy is defined as the treatment of disease by transfer of genetic material into cells. This review will explore methods available for gene transfer as well as current and potential applications for craniofacial regeneration, with emphasis on future development and design. Though non-viral gene delivery methods are limited by low gene transfer efficiency, they benefit from relative safety, low immunogenicity, ease of manufacture, and lack of DNA insert size limitation. In contrast, viral vectors are nature’s gene delivery machines that can be optimized to allow for tissue-specific targeting, site-specific chromosomal integration, and efficient long-term infection of dividing and non-dividing cells. In contrast to traditional replacement gene therapy, craniofacial regeneration seeks to use genetic vectors as supplemental building blocks for tissue growth and repair. Synergistic combination of viral gene therapy with craniofacial tissue engineering will significantly enhance our ability to repair and replace tissues in vivo.

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 Polymeric Nanoparticles in Gene Therapy: New Avenues of Design and Optimization for Delivery Applications

Polymers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 745 ◽  
Author(s):  
Raj Rai ◽  
Saniya Alwani ◽  
Ildiko Badea
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Targeted Delivery ◽  
Polymeric Nanoparticles ◽  
Genetic Material ◽  
Delivery Systems ◽  
Viral Gene ◽  
Cationic Polymers ◽  
Natural Polymers ◽  
Viral Gene Delivery

The field of polymeric nanoparticles is quickly expanding and playing a pivotal role in a wide spectrum of areas ranging from electronics, photonics, conducting materials, and sensors to medicine, pollution control, and environmental technology. Among the applications of polymers in medicine, gene therapy has emerged as one of the most advanced, with the capability to tackle disorders from the modern era. However, there are several barriers associated with the delivery of genes in the living system that need to be mitigated by polymer engineering. One of the most crucial challenges is the effectiveness of the delivery vehicle or vector. In last few decades, non-viral delivery systems have gained attention because of their low toxicity, potential for targeted delivery, long-term stability, lack of immunogenicity, and relatively low production cost. In 1987, Felgner et al. used the cationic lipid based non-viral gene delivery system for the very first time. This breakthrough opened the opportunity for other non-viral vectors, such as polymers. Cationic polymers have emerged as promising candidates for non-viral gene delivery systems because of their facile synthesis and flexible properties. These polymers can be conjugated with genetic material via electrostatic attraction at physiological pH, thereby facilitating gene delivery. Many factors influence the gene transfection efficiency of cationic polymers, including their structure, molecular weight, and surface charge. Outstanding representatives of polymers that have emerged over the last decade to be used in gene therapy are synthetic polymers such as poly(l-lysine), poly(l-ornithine), linear and branched polyethyleneimine, diethylaminoethyl-dextran, poly(amidoamine) dendrimers, and poly(dimethylaminoethyl methacrylate). Natural polymers, such as chitosan, dextran, gelatin, pullulan, and synthetic analogs, with sophisticated features like guanidinylated bio-reducible polymers were also explored. This review outlines the introduction of polymers in medicine, discusses the methods of polymer synthesis, addressing top down and bottom up techniques. Evaluation of functionalization strategies for therapeutic and formulation stability are also highlighted. The overview of the properties, challenges, and functionalization approaches and, finally, the applications of the polymeric delivery systems in gene therapy marks this review as a unique one-stop summary of developments in this field.

Viral vectors for gene delivery and gene therapy within the endocrine system

2000 ◽  
Vol 164 (2) ◽  
pp. 103-118 ◽  
Author(s):  
D Stone ◽  
A David ◽  
F Bolognani ◽  
PR Lowenstein ◽  
MG Castro
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vector ◽  
Genetic Material ◽  
Endocrine System ◽  
Endocrine Disorders ◽  
Advantages And Disadvantages ◽  
Vector Systems

The transfer of genetic material into endocrine cells and tissues, both in vitro and in vivo, has been identified as critical for the study of endocrine mechanisms and the future treatment of endocrine disorders. Classical methods of gene transfer, such as transfection, are inefficient and limited mainly to delivery into actively proliferating cells in vitro. The development of viral vector gene delivery systems is beginning to circumvent these initial setbacks. Several kinds of viruses, including retrovirus, adenovirus, adeno-associated virus, and herpes simplex virus, have been manipulated for use in gene transfer and gene therapy applications. As different viral vector systems have their own unique advantages and disadvantages, they each have applications for which they are best suited. This review will discuss viral vector systems that have been used for gene transfer into the endocrine system, and recent developments in viral vector technology that may improve their use for endocrine applications - chimeric vectors, viral vector targeting and transcriptional regulation of transgene expression.

scholarly journals Pulmonary gene delivery—Realities and possibilities

2020 ◽  
pp. 153537022096598
Author(s):  
Uday K Baliga ◽  
David A Dean
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Extracellular Vesicles ◽  
Viral Vectors ◽  
Neutral Lipids ◽  
Genetic Material ◽  
Building Blocks ◽  
Electrical Pulses ◽  
Primary Focus

Delivery of genetic material to tissues in vivo is an important technique used in research settings and is the foundation upon which clinical gene therapy is built. The lung is a prime target for gene delivery due to a host of genetic, acquired, and infectious diseases that manifest themselves there, resulting in many pathologies. However, the in vivo delivery of genetic material to the lung remains a practical problem clinically and is considered the major obstacle needed to be overcome for gene therapy. Currently there are four main strategies for in vivo gene delivery to the lung: viral vectors, liposomes, nanoparticles, and electroporation. Viral delivery uses several different genetically modified viruses that enter the cell and express desired genes that have been inserted to the viral genome. Liposomes use combinations of charged and neutral lipids that can encapsulate genetic cargo and enter cells through endogenous mechanisms, thereby delivering their cargoes. Nanoparticles are defined by their size (typically less than 100 nm) and are made up of many different classes of building blocks, including biological and synthetic polymers, cell penetrant and other peptides, and dendrimers, that also enter cells through endogenous mechanisms. Electroporation uses mild to moderate electrical pulses to create pores in the cell membrane through which delivered genetic material can enter a cell. An emerging fifth category, exosomes and extracellular vesicles, may have advantages of both viral and non-viral approaches. These extracellular vesicles bud from cellular membranes containing receptors and ligands that may aid cell targeting and which can be loaded with genetic material for efficient transfer. Each of these vectors can be used for different gene delivery applications based on mechanisms of action, side-effects, and other factors, and their use in the lung and possible clinical considerations is the primary focus of this review.

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

scholarly journals Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1964
Author(s):  
Huaiying Zhang ◽  
Damla Keskin ◽  
Willy H. de Haan-Visser ◽  
Guangyue Zu ◽  
Patrick van Rijn ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Tertiary Amine ◽  
Quaternary Ammonium ◽  
Gene Transfection ◽  
Genetic Material ◽  
Cationic Lipid ◽  
Endosomal Escape ◽  
Hereditary Diseases ◽  
Viral Gene

Gene therapy is a promising treatment for hereditary diseases, as well as acquired genetic diseases, including cancer. Facing the complicated physiological and pathological environment in vivo, developing efficient non-viral gene vectors is needed for their clinical application. Here, poly(N-isopropylacrylamide) (p(NIPAM)) nanogels are presented with either protonatable tertiary amine groups or permanently charged quaternized ammonium groups to achieve DNA complexation ability. In addition, a quaternary ammonium-functionalized nanogel was further provided with an aliphatic moiety using 1-bromododecane to add a membrane-interacting structure to ultimately facilitate intracellular release of the genetic material. The ability of the tertiary amine-, quaternized ammonium-, and aliphatic quaternized ammonium-functionalized p(NIPAM) nanogels (i.e., NGs, NGs-MI, and NGs-BDD, respectively) to mediate gene transfection was evaluated by fluorescence microscopy and flow cytometry. It is observed that NGs-BDD/pDNA complexes exhibit efficient gene loading, gene protection ability, and intracellular uptake similar to that of NGs-MI/pDNA complexes. However, only the NGs-BDD/pDNA complexes show a notable gene transfer efficiency, which can be ascribed to their ability to mediate DNA escape from endosomes. We conclude that NGs-BDD displays a cationic lipid-like behavior that facilitates endosomal escape by perturbing the endosomal/lysosomal membrane. These findings demonstrate that the presence of aliphatic chains within the nanogel is instrumental in accomplishing gene delivery, which provides a rationale for the further development of nanogel-based gene delivery systems.

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 Pharmacological, Cell, and Gene Therapy Strategies to Promote Spinal Cord Regeneration

2002 ◽  
Vol 11 (6) ◽  
pp. 593-613 ◽  
Author(s):  
Bas Blits ◽  
Gerard J. Boer ◽  
Joost Verhaagen
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Nervous System ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Cell Transplantation ◽  
Ex Vivo ◽  
Neuronal Survival ◽  
Genetically Modified ◽  
Injured Spinal Cord

In this review, recent studies using pharmacological treatment, cell transplantation, and gene therapy to promote regeneration of the injured spinal cord in animal models will be summarized. Pharmacological and cell transplantation treatments generally revealed some degree of effect on the regeneration of the injured ascending and descending tracts, but further improvements to achieve a more significant functional recovery are necessary. The use of gene therapy to promote repair of the injured nervous system is a relatively new concept. It is based on the development of methods for delivering therapeutic genes to neurons, glia cells, or nonneural cells. Direct in vivo gene transfer or gene transfer in combination with (neuro)transplantation (ex vivo gene transfer) appeared powerful strategies to promote neuronal survival and axonal regrowth following traumatic injury to the central nervous system. Recent advances in understanding the cellular and molecular mechanisms that govern neuronal survival and neurite outgrowth have enabled the design of experiments aimed at viral vector-mediated transfer of genes encoding neurotrophic factors, growth-associated proteins, cell adhesion molecules, and antiapoptotic genes. Central to the success of these approaches was the development of efficient, nontoxic vectors for gene delivery and the acquirement of the appropriate (genetically modified) cells for neurotransplantation. Direct gene transfer in the nervous system was first achieved with herpes viral and E1-deleted adenoviral vectors. Both vector systems are problematic in that these vectors elicit immunogenic and cytotoxic responses. Adeno-associated viral vectors and lentiviral vectors constitute improved gene delivery systems and are beginning to be applied in neuroregeneration research of the spinal cord. Ex vivo approaches were initially based on the implantation of genetically modified fibroblasts. More recently, transduced Schwann cells, genetically modified pieces of peripheral nerve, and olfactory ensheathing glia have been used as implants into the injured spinal cord.

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