scholarly journals Development of Viral Vectors for Gene Therapy for Chronic Pain

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
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.

scholarly journals Targeted Gene Delivery through the Respiratory System: Rationale for Intratracheal Gene Transfer

2019 ◽  
Vol 6 (1) ◽  
pp. 8 ◽  
Author(s):  
Michael Katz ◽  
Anthony Fargnoli ◽  
Sarah Gubara ◽  
Kenneth Fish ◽  
Thomas Weber ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Cell Types ◽  
Normal Lung ◽  
Target Cells ◽  
Specific Cell ◽  
Large Animal ◽  
Large Animal Models ◽  
Dna And Rna

Advances in DNA- and RNA-based technologies have made gene therapy suitable for many lung diseases, especially those that are hereditary. The main objective of gene therapy is to deliver an adequate amount of gene construct to the intended target cell, achieve stable transduction in target cells, and to produce a clinically therapeutic effect. This review focuses on the cellular organization in the normal lung and how gene therapy targets the specific cell types that are affected by pulmonary disorders caused by genetic mutations. Furthermore, it examines the pulmonary barriers that can compromise the absorption and transduction of viral vectors and genetic agents by the lung. Finally, it discusses the advantages and limitations of direct intra-tracheal gene delivery with different viral vectors in small and large animal models and in clinical trials.

scholarly journals Planet of the AAVs: The Spinal Cord Injury Episode

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 613
Author(s):  
Katerina Stepankova ◽  
Pavla Jendelova ◽  
Lucia Machova Urdzikova
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Cell Types ◽  
Specific Cell ◽  
Adeno Associated Virus ◽  
Adequate Treatment ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Transgene Delivery

The spinal cord injury (SCI) is a medical and life-disrupting condition with devastating consequences for the physical, social, and professional welfare of patients, and there is no adequate treatment for it. At the same time, gene therapy has been studied as a promising approach for the treatment of neurological and neurodegenerative disorders by delivering remedial genes to the central nervous system (CNS), of which the spinal cord is a part. For gene therapy, multiple vectors have been introduced, including integrating lentiviral vectors and non-integrating adeno-associated virus (AAV) vectors. AAV vectors are a promising system for transgene delivery into the CNS due to their safety profile as well as long-term gene expression. Gene therapy mediated by AAV vectors shows potential for treating SCI by delivering certain genetic information to specific cell types. This review has focused on a potential treatment of SCI by gene therapy using AAV vectors.

scholarly journals Cellular Circuits in the Brain and Their Modulation in Acute and Chronic Pain

2021 ◽  
Vol 101 (1) ◽  
pp. 213-258 ◽  
Author(s):  
Rohini Kuner ◽  
Thomas Kuner
Keyword(s):  
Chronic Pain ◽  
Neural Circuits ◽  
Cell Types ◽  
Mammalian Brain ◽  
Specific Cell ◽  
Dynamic Regulation ◽  
Maladaptive Plasticity ◽  
Pathological Pain ◽  
Dimensions Of Pain ◽  
Cellular Circuits

Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle to preventing, treating, or reverting chronic pain has been that the nature of neural circuits underlying the diverse components of the complex, multidimensional experience of pain is not well understood. Moreover, chronic pain involves diverse maladaptive plasticity processes, which have not been decoded mechanistically in terms of involvement of specific circuits and cause-effect relationships. This review aims to discuss recent advances in our understanding of circuit connectivity in the mammalian brain at the level of regional contributions and specific cell types in acute and chronic pain. A major focus is placed on functional dissection of sub-neocortical brain circuits using optogenetics, chemogenetics, and imaging technological tools in rodent models with a view towards decoding sensory, affective, and motivational-cognitive dimensions of pain. The review summarizes recent breakthroughs and insights on structure-function properties in nociceptive circuits and higher order sub-neocortical modulatory circuits involved in aversion, learning, reward, and mood and their modulation by endogenous GABAergic inhibition, noradrenergic, cholinergic, dopaminergic, serotonergic, and peptidergic pathways. The knowledge of neural circuits and their dynamic regulation via functional and structural plasticity will be beneficial towards designing and improving targeted therapies.

scholarly journals Current Gene Therapy using Viral Vectors for Chronic Pain

2015 ◽  
Vol 11 ◽  
pp. s12990-015-0018 ◽  
Author(s):  
Jean-Marc G Guedon ◽  
Shaogen Wu ◽  
Xuexing Zheng ◽  
Caroline C Churchill ◽  
Joseph C Glorioso ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Chronic Pain ◽  
Viral Vectors

scholarly journals Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation

2019 ◽  
Author(s):  
Leila Haery ◽  
Benjamin E. Deverman ◽  
Katherine Matho ◽  
Ali Cetin ◽  
Kenton Woodard ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Cell Types ◽  
Regulatory Elements ◽  
Specific Cell ◽  
Specific Expression ◽  
Adeno Associated Virus ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
And Function ◽  
Novel Applications

AbstractCell-type-specific expression of molecular tools and sensors is critical to construct circuit diagrams and to investigate the activity and function of neurons within the nervous system. Strategies for targeted manipulation include combinations of classical genetic tools such as Cre/loxP and Flp/FRT, use of cis-regulatory elements, targeted knock-in transgenic mice, and gene delivery by AAV and other viral vectors. The combination of these complex technologies with the goal of precise neuronal targeting is a challenge in the lab. This report will discuss the theoretical and practical aspects of combining current technologies and establish best practices for achieving targeted manipulation of specific cell types. Novel applications and tools, as well as areas for development, will be envisioned and discussed.

scholarly journals Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ

Biology Open ◽  
2021 ◽  
Author(s):  
E.S. Zubkova ◽  
I.B. Beloglazova ◽  
E.I. Ratner ◽  
D.T. Dyikanov ◽  
K.V. Dergilev ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cellular Response ◽  
Viral Vectors ◽  
Viral Vector ◽  
Ex Vivo ◽  
Human Adipose Tissue ◽  
Cell Types ◽  
Specific Cell ◽  
Therapeutic Benefits ◽  
Rat Adipose Tissue

Ex vivo, gene therapy is a powerful approach holding great promises for the treatment of both genetic and acquired diseases. Adeno-associated virus (AAV) vectors are safe and efficient delivery system for modification of mesenchymal stem cells (MSC) that could maximize their therapeutic benefits. Assessment to MSC viability and functional activity after infection with new AAV serotypes is necessary, due to AAV tropism to specific cell types. We infected human and rat adipose-tissue MSC with hybrid AAV-DJ serotype vectors carrying GFP and SCF genes. GFP expression from AAV-DJ was about 1.5-fold superior to that observed with AAV-2 and lasted for at least 21 days as was evaluated by flow cytometry and fluorescence microscopy. AAV-DJ proves to be suitable for the infection of rat and human MSC with a similar efficiency. Infected MSC were still viable however showing 25-30%. growth rate slowdown. Moreover, we found increase of SERPINB2 mRNA expression in human MSC whereas expression of other oxidative stress markers and extracellular matrix proteins was not affected. These results suggest that there is a differential cellular response in MSC infected with AAV viral vectors, which should be taken into account as it can affect the expected outcome for the therapeutic application.

scholarly journals Dynamics of Breast Cancer under Different Rates of Chemoradiotherapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Sara B. Mkango ◽  
Nyimvua Shaban ◽  
Eunice Mureithi ◽  
Twalib Ngoma
Keyword(s):  
Breast Cancer ◽  
Gene Therapy ◽  
Decay Rate ◽  
Hormone Therapy ◽  
Cause Of Death ◽  
Breast Tissue ◽  
Treatment Strategies ◽  
Common Cause ◽  
New Treatment ◽  
Treat Breast Cancer

A type of cancer which originates from the breast tissue is referred to as breast cancer. Globally, it is the most common cause of death in women. Treatments such as radiotherapy, chemotherapy, hormone therapy, immunotherapy, and gene therapy are the main strategies in the fight against breast cancer. The present study aims at investigating the effects of the combined radiotherapy and chemotherapy as a way to treat breast cancer, and different treatment approaches are incorporated into the model. Also, the model is fitted to data on patients with breast cancer in Tanzania. We determine new treatment strategies, and finally, we show that when sufficient amount of chemotherapy and radiotherapy with a low decay rate is used, the drug will be significantly more effective in combating the disease while health cells remain above the threshold.

scholarly journals Pain Perception and Management: Where Are We Standing

2020 ◽  
Vol 13 ◽  
Author(s):  
Bilal Afridi ◽  
Haroon Khan ◽  
Esra Kupeli Akkol
Keyword(s):  
Inflammatory Pain ◽  
Pain Perception ◽  
Treatment Strategies ◽  
Research Field ◽  
Human Beings ◽  
Electrical Shock ◽  
Chemical Mechanisms ◽  
Pain Pathways ◽  
New Treatment ◽  
The Individual

Background: Pain is often flammable, sharp and sometimes described as an electrical shock and can be categorized in three different ways as nociceptive, neuropathic and inflammatory. Nociceptive always originates in specific situations like in case of trauma. Neuropathic pain results in the case of nerve damage and inflammatory pain. In inflammatory pain, inflammatory mediators are involved in the sensitization of nociceptors. It is important to control the pain as it affects the individual physically, mentally, and socially. Objective: Knowing the pain physiopathology and pain pathways, defining the relationship between receptor and transmitter is very important in determining new treatment strategies. In this review, current information on the definitions, classifications, and physiological and chemical mechanisms involved in pain are reviewed. Methods: Different search engines were used to gather related articles/information. All those journals which are peerreviewed were considered. Additional, books/chapters of standard publishers were also included in the article. Results: In recent years, with a better understanding of the physiological and chemical mechanisms that play a role in pain, significant improvements have been achieved in the treatment of pain. Various oral or intravenous drugs, local injection treatments, physical and occupational therapy, electrical stimulation, alternative medicine applications, psychological support, and surgical applications are performed in the treatment depending on the severity or the cause of the pain. Conclusions: The development and renewal of the knowledge about pain physiopathology can be the basis for improving the quality of life of human beings and providing effective and reliable treatments with technological elements developing in the clinical and research field.

scholarly journals Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates, and humans

2018 ◽  
Author(s):  
Josephine Jüttner ◽  
Arnold Szabo ◽  
Brigitte Gross-Scherf ◽  
Rei K. Morikawa ◽  
Santiago B. Rompani ◽  
...  
Keyword(s):  
Glial Cell ◽  
Viral Vectors ◽  
Cell Types ◽  
Mouse Retina ◽  
Specific Cell ◽  
Synthetic Promoter ◽  
Brain Circuits ◽  
Human Primate

SummaryTargeting genes to specific neuronal or glial cell types is valuable both for understanding and for repairing brain circuits. Adeno-associated viral vectors (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is a challenge. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that ~11% of these AAVs specifically target expression to neuronal and glial cell types in the mouse retina, mouse brain, non-human primate retinain vivo, and in the human retinain vitro. We demonstrate applications for recording, stimulation, and molecular characterization, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast, and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.

scholarly journals Viruses in the Mammalian Male Genital Tract and Their Effects on the Reproductive System

2001 ◽  
Vol 65 (2) ◽  
pp. 208-231 ◽  
Author(s):  
Nathalie Dejucq ◽  
Bernard Jégou
Keyword(s):  
Reproductive Tract ◽  
Viral Infections ◽  
Treatment Strategies ◽  
Endocrine System ◽  
Induced Mutations ◽  
Research Strategies ◽  
Testicular Cells ◽  
Functional Consequences ◽  
New Treatment ◽  
The Individual

SUMMARY This review describes the various viruses identified in the semen and reproductive tracts of mammals (including humans), their distribution in tissues and fluids, their possible cell targets, and the functional consequences of their infectivity on the reproductive and endocrine systems. The consequences of these viral infections on the reproductive tract and semen can be extremely serious in terms of organ integrity, development of pathological and cancerous processes, and transmission of diseases. Furthermore, of essential importance is the fact that viral infection of the testicular cells may result not only in changes in testicular function, a serious risk for the fertility and general health of the individual (such as a fall in testosteronemia leading to cachexia), but also in the possible transmission of virus-induced mutations to subsequent generations. In addition to providing an exhaustive account of the data available in these domains, this review focuses attention on the fact that the interface between endocrinology and virology has so far been poorly explored, particularly when major health, social and economical problems are posed. Our conclusions highlight the research strategies that need to be developed. Progress in all these domains is essential for the development of new treatment strategies to eradicate viruses and to correct the virus-induced dysfunction of the endocrine system.

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