scholarly journals Prolonged expression of a lysosomal enzyme in mouse liver afterSleeping Beauty transposon-mediated gene delivery: implications for non-viral gene therapy of mucopolysaccharidoses

2007 ◽  
Vol 9 (5) ◽  
pp. 403-415 ◽  
Author(s):  
Elena L. Aronovich ◽  
Jason B. Bell ◽  
Lalitha R. Belur ◽  
Roland Gunther ◽  
Brenda Koniar ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Lysosomal Enzyme ◽  
Mouse Liver ◽  
Viral Gene ◽  
Viral Gene Therapy

scholarly journals Non-viral Gene Therapy for Osteoarthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Ilona Uzieliene ◽  
Ursule Kalvaityte ◽  
Eiva Bernotiene ◽  
Ali Mobasheri
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Articular Chondrocytes ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Synovial Joint ◽  
Advantages And Disadvantages ◽  
Viral Gene Therapy ◽  
Viral Gene Delivery ◽  
Significant Effort

Strategies for delivering nucleic acids into damaged and diseased tissues have been divided into two major areas: viral and non-viral gene therapy. In this mini-review article we discuss the application of gene therapy for the treatment of osteoarthritis (OA), one of the most common forms of arthritis. We focus primarily on non-viral gene therapy and cell therapy. We briefly discuss the advantages and disadvantages of viral and non-viral gene therapy and review the nucleic acid transfer systems that have been used for gene delivery into articular chondrocytes in cartilage from the synovial joint. Although viral gene delivery has been more popular due to its reported efficiency, significant effort has gone into enhancing the transfection efficiency of non-viral delivery, making non-viral approaches promising tools for further application in basic, translational and clinical studies on OA. Non-viral gene delivery technologies have the potential to transform the future development of disease-modifying therapeutics for OA and related osteoarticular disorders. However, further research is needed to optimize transfection efficiency, longevity and duration of gene expression.

Polyamines and novel polyamine conjugates interact with DNA in ways that can be exploited in non-viral gene therapy

2003 ◽  
Vol 31 (2) ◽  
pp. 397-406 ◽  
Author(s):  
I.S. Blagbrough ◽  
A.J. Geall ◽  
A.P. Neal
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Rational Design ◽  
Molecular Probes ◽  
Dna Condensation ◽  
Viral Gene ◽  
Viral Gene Therapy ◽  
Lipid Moiety ◽  
Polyamine Conjugates ◽  
Fluorescent Molecular Probes

As a part of our continuing studies on ‘Polyamines and their role in human disease’ we are investigating how polyamines, and especially how novel polyamine conjugates, interact with DNA. We are studying how these conjugates interact with circular plasmids in order to produce nanometre-sized particles suitable for transfecting cells. Our considerations of structure--activity relationships (SAR) within naturally occurring and synthetic polyamines have shown the significance of the inter-atomic distances between the basic nitrogen atoms. As these atoms are typically fully protonated under physiological conditions, they exist in equilibrium as polyammonium ions. The covalent addition of a lipid moiety, typically one or two alkyl or alkenyl chains, or a steroid, allows much greater efficiency in DNA condensation and in the cellular transfection achieved. Thus efficient DNA condensation and subsequently drug delivery (i.e. with DNA as the drug) can be brought about using novel polyamine conjugates. Taking further advantage of the functionalization of specific steroids (e.g. cholesterol and certain bile acids), we have designed and prepared novel fluorescent molecular probes as tools to throw light on the problematic steps in non-viral gene delivery which still impede efficient gene therapy. Thus, the current aims of our research are to understand, design and prepare small-molecule lipopolyamines for non-viral gene therapy (NVGT). The rational design and practical preparation of non-symmetrical polyamine carbamates and amides, based on steroid templates of cholesterol and the bile acid lithocholic acid as the lipid moiety, provides fluorescent molecular probes that condense DNA. These novel lipopolyamine conjugates mimic the positive charge distribution found in the triamine spermidine and the tetra-amine spermine alkaloids. After optimizing their SAR, these fluorescent probes will be useful in monitoring gene delivery in NVGT.

scholarly journals Balancing protection and release of DNA: tools to address a bottleneck of non-viral gene delivery

2009 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Christopher L. Grigsby ◽  
Kam W. Leong
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Imaging Techniques ◽  
Model Systems ◽  
Viral Gene ◽  
Dna Protection ◽  
Gene Delivery Vectors ◽  
Viral Gene Therapy ◽  
Polymeric Gene Delivery

Engineering polymeric gene-delivery vectors to release an intact DNA payload at the optimal time and subcellular compartment remains a formidable challenge. An ideal vector would provide total protection of complexed DNA from degradation prior to releasing it efficiently near or within the nucleus of a target cell. While optimization of polymer properties, such as molecular weight and charge density, has proved largely inadequate in addressing this challenge, applying polymeric carriers that respond to temperature, light, pH and redox environment to trigger a switch from a tight, protective complex to a more relaxed interaction favouring release at the appropriate time and place has shown promise. Currently, a paucity of gene carriers able to satisfy the contrary requirements of adequate DNA protection and efficient release contributes to the slow progression of non-viral gene therapy towards clinical translation. This review highlights the promising carrier designs that may achieve an optimal balance of DNA protection and release. It also discusses the imaging techniques and three-dimensional in vitro models that can help study these two barriers in the non-viral gene transfer process. Ultimately, efficacious non-viral gene therapy will depend on the combination of intelligent material design, innovative imaging techniques and sophisticated in vitro model systems to facilitate the rational design of polymeric gene-delivery vectors.

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 α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 771
Author(s):  
Julen Rodríguez-Castejón ◽  
Ana Alarcia-Lacalle ◽  
Itziar Gómez-Aguado ◽  
Mónica Vicente-Pascual ◽  
María Ángeles Solinís Aspiazu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Fabry Disease ◽  
Viral Vector ◽  
Viral Gene ◽  
Lysosomal Storage ◽  
Wild Type ◽  
Dose Administration ◽  
Viral Gene Therapy ◽  
Liver Transaminases ◽  
Low Levels

Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.

Long‐term functional correction of cystathionine β‐synthase deficiency in mice by adeno‐associated viral gene therapy

2021 ◽  
Author(s):  
Hyung‐Ok Lee ◽  
Christiana O. Salami ◽  
Dolan Sondhi ◽  
Stephen M. Kaminsky ◽  
Ronald G. Crystal ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Viral Gene ◽  
Functional Correction ◽  
Viral Gene Therapy

scholarly journals Recognition of Virus Infection and Innate Host Responses to Viral Gene Therapy Vectors

2010 ◽  
Vol 18 (8) ◽  
pp. 1422-1429 ◽  
Author(s):  
Dmitry M Shayakhmetov ◽  
Nelson C Di Paolo ◽  
Karen L Mossman
Keyword(s):  
Gene Therapy ◽  
Virus Infection ◽  
Host Responses ◽  
Viral Gene ◽  
Viral Gene Therapy ◽  
Gene Therapy Vectors

scholarly journals Delivery of modified mRNA encoding vesicular stomatitis virus matrix protein for colon cancer gene therapy

RSC Advances ◽  
2018 ◽  
Vol 8 (22) ◽  
pp. 12104-12115 ◽  
Author(s):  
Ke Men ◽  
Rui Zhang ◽  
Xueyan Zhang ◽  
Rong Huang ◽  
Guonian Zhu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Colon Cancer ◽  
Colon Carcinoma ◽  
Vesicular Stomatitis Virus ◽  
Matrix Protein ◽  
Cancer Gene Therapy ◽  
Viral Gene ◽  
Cancer Gene ◽  
Viral Gene Therapy ◽  
Vesicular Stomatitis

Liposome–protamine complex delivered VSVMP mRNA efficiently inhibits C26 colon carcinoma with safety, providing an alternative strategy for non-viral gene therapy.

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