A Review of Gene Therapy Delivery Systems for Intervertebral Disc Degeneration

Background: : Intervertebral Disc (IVD) degeneration is a major public health concern, and gene therapy seems a promising approach to delay or even reverse IVD degeneration. However, the delivery system used to transfer exogenous genes into intervertebral disc cells remains a challenge. Methods:: The MEDLINE, Web of Science, and Scopus databases were searched for English-language articles related to gene therapy for IVD degeneration articles from 1999 to May 2019. The keywords included “gene therapy” AND “intervertebral disc”. The history of the development of different delivery systems was analysed, and the latest developments in viral and non-viral vectors for IVD degeneration treatment were reviewed. Results: : Gene therapy delivery systems for IVD degeneration are divided into two broad categories: viral and non-viral vectors. The most commonly used viral vectors are adenovirus, adeno-associated virus (AAV), and lentivirus. Enthusiasm for the use of adenovirus vectors has gradually declined and has been replaced by a preference for lentivirus and AAV vectors. New technologies, such as RNAi and CRISPR, have further enhanced the advantage of viral vectors. Liposomes are the classic non-viral vector, and their successors, polyplex micelles and exosomes, have more potential for use in gene therapy for IVD degeneration. Conclusion:: Lentivirus and AAV are the conventional viral vectors used in gene therapy for IVD degeneration, and the new technologies RNAi and CRISPR have further enhanced their advantages. Nonviral vectors, such as polyplex micelles and exosomes, are promising gene therapy vectors for IVD degeneration.

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The Role of New Technologies to Prevent Suicide in Adolescence: A Systematic Review of the Literature

Medicina ◽

10.3390/medicina57020109 ◽

2021 ◽

Vol 57 (2) ◽

pp. 109

Author(s):

Alberto Forte ◽

Giuseppe Sarli ◽

Lorenzo Polidori ◽

David Lester ◽

Maurizio Pompili

Keyword(s):

Suicide Prevention ◽

Mobile Applications ◽

English Language ◽

New Technologies ◽

Cross Sectional Study ◽

Text Messages ◽

Health Concern ◽

Preventive Strategies ◽

Open Label ◽

Cross Sectional

Background and objectives: Suicide in adolescents represents a major public health concern. To date, a growing number of suicide preventive strategies based on the use of new technologies are emerging. We aimed to provide an overview of the present literature on the use of new technologies in adolescent suicide prevention. Materials and methods: An electronic search was run using the following keywords: Technology OR Technologies OR APP OR Application OR mobile application) AND (Adolescent OR youth OR puberty) AND (Suicid* OR Self-harm OR self-destruction). Inclusion criteria were: English language, published in a peer-reviewed journal, suicide prevention with the use of new technologies among adolescents. Results: Our search strategy yielded a total of 12 studies on the use of telemedicine, 7 on mobile applications, and 3 on language detection. We also found heterogeneity regarding the study design: 3 are randomized controlled trials (RCT), 13 are open-label single group trials, 2 are randomized studies, and 1 is a cross-sectional study. Telemedicine was the most adopted tool, especially web-based approaches. Mobile applications mostly focused on screening of depressive symptoms and suicidal ideation, and for clinical monitoring through the use of text messages. Although telepsychiatry and mobile applications can provide a fast and safe tool, supporting and preceding a face-to-face clinical assessment, only a few studies demonstrated efficacy in preventing suicide among adolescents through the use of these interventions. Some studies suggested algorithms able to recognize people at risk of suicide from the exploration of the language on social media posts. Conclusions: New technologies were found to be well accepted and tolerated supports for suicide prevention in adolescents. However, to date, few data support the use of such interventions in clinical practice and preventive strategies. Further studies are needed to test their efficacy in suicide prevention among adolescents and young adults.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22147545 ◽

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.

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

Pharmaceutics ◽

10.3390/pharmaceutics12121219 ◽

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.

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Adeno-Associated Viral Vectors for Gene Transfer and Gene Therapy

Biological Chemistry ◽

10.1515/bc.1999.078 ◽

1999 ◽

Vol 380 (6) ◽

Cited By ~ 63

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

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Gene Therapy Delivery Systems for Enhancing Viral and Nonviral Vectors for Cardiac Diseases: Current Concepts and Future Applications

Human Gene Therapy ◽

10.1089/hum.2013.2517 ◽

2013 ◽

Vol 24 (11) ◽

pp. 914-927 ◽

Cited By ~ 38

Author(s):

Michael G. Katz ◽

Anthony S. Fargnoli ◽

Richard D. Williams ◽

Charles R. Bridges

Keyword(s):

Gene Therapy ◽

Delivery Systems ◽

Cardiac Diseases ◽

Nonviral Vectors ◽

Therapy Delivery

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Gene therapy for neurodegenerative and ocular diseases using lentiviral vectors

Clinical Science ◽

10.1042/cs20050158 ◽

2005 ◽

Vol 110 (1) ◽

pp. 37-46 ◽

Cited By ~ 22

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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Development of Viral Vectors for Gene Therapy for Chronic Pain

Pain Research and Treatment ◽

10.1155/2011/968218 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Yu Huang ◽

Xin Liu ◽

Lanlan Dong ◽

Zhongchun Liu ◽

Xiaohua He ◽

...

Keyword(s):

Gene Therapy ◽

Chronic Pain ◽

Viral Vectors ◽

Treatment Strategies ◽

Opioid Analgesics ◽

Cell Types ◽

Health Concern ◽

Specific Cell ◽

New Treatment ◽

The Individual

Chronic pain is a major health concern that affects millions of people. There are no adequate long-term therapies for chronic pain sufferers, leading to significant cost for both society and the individual. The most commonly used therapy for chronic pain is the application of opioid analgesics and nonsteroidal anti-inflammatory drugs, but these drugs can lead to addiction and may cause side effects. Further studies of the mechanisms of chronic pain have opened the way for development of new treatment strategies, one of which is gene therapy. The key to gene therapy is selecting safe and highly efficient gene delivery systems that can deliver therapeutic genes to overexpress or suppress relevant targets in specific cell types. Here we review several promising viral vectors that could be applied in gene transfer for the treatment of chronic pain and further discuss the possible mechanisms of genes of interest that could be delivered with viral vectors for the treatment of chronic pain.

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

10.46619/cmj.2019.2-1007 ◽

2019 ◽

Vol 2 (1) ◽

pp. 6-13 ◽

Cited By ~ 1

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.

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Gene Therapy Approaches

Qubahan Academic Journal ◽

10.48161/qaj.v1n1a35 ◽

2021 ◽

Vol 1 (1) ◽

pp. 52-56

Author(s):

Hogir Saadi

Keyword(s):

Gene Therapy ◽

Viral Vectors ◽

Nuclear Translocation ◽

Viral Vector ◽

Ex Vivo ◽

Genetic Material ◽

Target Tissue ◽

Human Beings ◽

Vector Systems

Gene therapy can be described broadly as the transfer of genetic material to control a disease or at least to enhance a patient's clinical status. The transformation of viruses into genetic shuttles is one of the core principles of gene therapy, which will introduce the gene of interest into the target tissue and cells. To do this, safe strategies have been invented, using many viral and non-viral vector delivery. Two major methods have emerged: modification in vivo and modification ex vivo. For gene therapeutic approaches which are focused on lifelong expression of the therapeutic gene, retrovirus, adenovirus, adeno-associated viruses are acceptable. Non-viral vectors are much less successful than viral vectors, but because of their low immune responses and their broad therapeutic DNA ability, they have advantages. The addition of viral functions such as receptor-mediated uptake and nuclear translocation of DNA may eventually lead to the development of an artificial virus in order to improve the role of non-viral vectors. For human use in genetic conditions, cancers and acquired illnesses, gene transfer techniques have been allowed. The ideal delivery vehicle has not been identified, although the accessible vector systems are capable of transporting genes in vivo into cells. Therefore, only with great caution can the present viral vectors be used in human beings and further progress in the production of vectors is required. Current progresses in our understanding of gene therapy approaches and their delivery technology, as well as the victors used to deliver therapeutic genes, are the primary goals of this review. For that reason, a literature search on PubMed and Google Scholar was carried out using different keywords.

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Advances in delivery vectors for gene therapy in liver cancer

Therapeutic Delivery ◽

10.4155/tde-2019-0076 ◽

2020 ◽

Vol 11 (1) ◽

pp. 833-850 ◽

Cited By ~ 5

Author(s):

Katherine E Redd Bowman ◽

Phong Lu ◽

Erica R Vander Mause ◽

Carol S Lim

Keyword(s):

Hepatocellular Carcinoma ◽

Gene Therapy ◽

Viral Vectors ◽

Gene Editing ◽

Cancer Death ◽

Common Cause ◽

The Third ◽

Gene Delivery Vectors ◽

Efficient Delivery ◽

Therapy Delivery

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death globally, mainly due to lack of effective treatments – a problem that gene therapy is poised to solve. Successful gene therapy requires safe and efficient delivery vectors, and recent advances in both viral and nonviral vectors have made an important impact on HCC gene therapy delivery. This review explores how adenoviral, retroviral and adeno-associated viral vectors have been modified to increase safety and delivery capacity, highlighting studies and clinical trials using these vectors for HCC gene therapy. Nanoparticles, liposomes, exosomes and virosomes are also featured in their roles as HCC gene delivery vectors. Finally, new discoveries in gene editing technology and their impacts on HCC gene therapy are discussed.

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