scholarly journals Gene Delivery Strategies to Promote Spinal Cord Repair

2015 ◽  
Vol 10s1 ◽  
pp. BMI.S20063 ◽  
Author(s):  
Christopher M. Walthers ◽  
Stephanie K. Seidlits
Keyword(s):  
Spinal Cord ◽  
Gene Delivery ◽  
Tissue Regeneration ◽  
Target Genes ◽  
Cell Types ◽  
Great Promise ◽  
Gene Therapies ◽  
The Central Nervous System ◽  
Transgene Delivery ◽  
Genetic Vectors

Gene therapies hold great promise for the treatment of many neurodegenerative disorders and traumatic injuries in the central nervous system. However, development of effective methods to deliver such therapies in a controlled manner to the spinal cord is a necessity for their translation to the clinic. Although essential progress has been made to improve efficiency of transgene delivery and reduce the immunogenicity of genetic vectors, there is still much work to be done to achieve clinical strategies capable of reversing neurodegeneration and mediating tissue regeneration. In particular, strategies to achieve localized, robust expression of therapeutic transgenes by target cell types, at controlled levels over defined time periods, will be necessary to fully regenerate functional spinal cord tissues. This review summarizes the progress over the last decade toward the development of effective gene therapies in the spinal cord, including identification of appropriate target genes, improvements to design of genetic vectors, advances in delivery methods, and strategies for delivery of multiple transgenes with synergistic actions. The potential of biomaterials to mediate gene delivery while simultaneously providing inductive scaffolding to facilitate tissue regeneration is also discussed.

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 Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Song Cao ◽  
Daniel W. Fisher ◽  
Guadalupe Rodriguez ◽  
Tian Yu ◽  
Hongxin Dong
Keyword(s):  
Spinal Cord ◽  
Locus Coeruleus ◽  
Microglial Activation ◽  
Healthy Aging ◽  
Cell Types ◽  
Norepinephrine System ◽  
Protective Processes ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Abstract Background The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. Methods In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Results Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. Conclusion These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

scholarly journals Current Status and Challenges Associated with CNS-Targeted Gene Delivery across the BBB

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1216
Author(s):  
Seigo Kimura ◽  
Hideyoshi Harashima
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Neurological Disorders ◽  
Viral Vectors ◽  
New Drugs ◽  
Brain Targeting ◽  
Current Status ◽  
Great Promise ◽  
Targeted Gene Delivery ◽  
The Central Nervous System

The era of the aging society has arrived, and this is accompanied by an increase in the absolute numbers of patients with neurological disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such neurological disorders are serious costly diseases that have a significant impact on society, both globally and socially. Gene therapy has great promise for the treatment of neurological disorders, but only a few gene therapy drugs are currently available. Delivery to the brain is the biggest hurdle in developing new drugs for the central nervous system (CNS) diseases and this is especially true in the case of gene delivery. Nanotechnologies such as viral and non-viral vectors allow efficient brain-targeted gene delivery systems to be created. The purpose of this review is to provide a comprehensive review of the current status of the development of successful drug delivery to the CNS for the treatment of CNS-related disorders especially by gene therapy. We mainly address three aspects of this situation: (1) blood-brain barrier (BBB) functions; (2) adeno-associated viral (AAV) vectors, currently the most advanced gene delivery vector; (3) non-viral brain targeting by non-invasive methods.

scholarly journals Chitosan Applications Used in Medical Therapy of Tissue Regeneration

2016 ◽  
Vol 2 (2) ◽  
pp. 271
Author(s):  
Alef Mustafa ◽  
Ana Maria Ionescu ◽  
Melat Cherim ◽  
Rodica Sîrbu
Keyword(s):  
Tissue Engineering ◽  
Tissue Regeneration ◽  
Biomedical Applications ◽  
Vascular Tissue ◽  
Bulk Material ◽  
Cell Types ◽  
Biological Molecules ◽  
Great Promise ◽  
Nucleus Pulposus Cells ◽  
Biological Specificity

Chitosan is an unique natural biopolymer that has great potential in tissue engineering applications and over the past several decades, it has emerged as a promising biomaterial for biomedical applications. Due to its various properties such as controllable biodegradability, biocompatibility, antimicrobial activity and functionalizability, chitosan can be used to form chitosan-based scaffolds and in different scaffold fabrication techniques. Over the years a great number of studies have been performed to evaluate the cytocompatibility of chitosan using a variety off cell types such as osteoblasts, chondrocytes, fibroblasts, nucleus pulposus cells, neutral and endothelial cells. It was shown that chitosan is biocompatible with these cell types and has the potential to be used for bone, cartilage, skin, intervertebral disc, ligament and tendon, and nerve and vascular tissue engineering. The flexibility of the processing conditions of chitosan aids in the fabrication of versatile substrates as scaffolds for tissue regeneration or carriers for biological molecules. It is critical to synthesize medical grade chitosan materials with controllable structure and properties that will allow the development of chitosan-based medical devices and it is beneficial to chemically design chitosan derivatives with molecular and biological specificity through bulk material modification. Despite all the challenges, chitosan holds great promise as a biomaterial for developing medical products and medical therapies.

scholarly journals High Numbers of Viral RNA Copies in the Central Nervous System of Mice during Persistent Infection with Theiler's Virus

2001 ◽  
Vol 75 (16) ◽  
pp. 7420-7428 ◽  
Author(s):  
Mark Trottier ◽  
Pat Kallio ◽  
Wei Wang ◽  
Howard L. Lipton
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Infectious Virus ◽  
Rna Replication ◽  
Cell Types ◽  
Viral Rna ◽  
Minus Strand ◽  
Viral Genomes ◽  
The Central Nervous System ◽  
Low Levels

ABSTRACT The low-neurovirulence Theiler's murine encephalomyelitis viruses (TMEV), such as BeAn virus, cause a persistent infection of the central nervous system (CNS) in susceptible mouse strains that results in inflammatory demyelination. The ability of TMEV to persist in the mouse CNS has traditionally been demonstrated by recovering infectious virus from the spinal cord. Results of infectivity assays led to the notion that TMEV persists at low levels. In the present study, we analyzed the copy number of TMEV genomes, plus- to minus-strand ratios, and full-length species in the spinal cords of infected mice and infected tissue culture cells by using Northern hybridization. Considering the low levels of infectious virus in the spinal cord, a surprisingly large number of viral genomes (mean of 3.0 × 109) was detected in persistently infected mice. In the transition from the acute (approximately postinfection [p.i.] day 7) to the persistent (beginning on p.i. day 28) phase of infection, viral RNA copy numbers steadily increased, indicating that TMEV persistence involves active viral RNA replication. Further, BeAn viral genomes were full-length in size; i.e., no subgenomic species were detected and the ratio of BeAn virus plus- to minus-strand RNA indicated that viral RNA replication is unperturbed in the mouse spinal cord. Analysis of cultured macrophages and oligodendrocytes suggests that either of these cell types can potentially synthesize high numbers of viral RNA copies if infected in the spinal cord and therefore account for the heavy viral load. A scheme is presented for the direct isolation of both cell types directly from infected spinal cords for further viral analyses.

Cardiac disease: Current approaches to gene therapy

2020 ◽  
pp. 62-75
Author(s):  
Reyad ul-ferdous ◽  
◽  
Shofiul Azam ◽  
◽  
◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Gene Delivery ◽  
Cardiac Disease ◽  
Target Genes ◽  
Viral Vector ◽  
Delivery Methods ◽  
Gene Therapies ◽  
Inherited Cardiomyopathies

Background: Last decade over the world, the cardiac disease becomes a leading cause of death. Gene-based therapies become a promising treatment for patients affected by cardiovascular diseases, such as myocardial infarction (MI), arteriosclerosis, heart failure and so on, but also underline the require for reproducible results in preclinical and clinical studies for efficacy and safety. Aim: This book chapter describes the current research prospect of gene therapy for cardiac disease. We focus on the various models to deliver genes using viral, non-viral vector, delivery methods, targets gene, recent clinical trials, inherited cardiomyopathies target genes and Present advances of CRISPR/Cas 9 for cardiovascular gene therapy. We recapitulate some challenges that require being overcome, future directions of gene therapies for cardiac disease. Materials and Methods: All required information regards Lef-7 was generated by exploring the internet search engine like as (PubMed, Wiley, ScienceDirect, CNKI, ACS, Google Scholar, Web of Science, SciFinder, and Baidu Scholar) and libraries. Results: In this book chapter, we focus on the present prospect of gene targets, gene delivery methods, and efficient vector to deliver gene, targets gene, recent clinical trials, inherited cardiomyopathies target genes and present advances of CRISPR/Cas 9 technology for the treatment of cardiac disease using gene therapy. Recent clinical trials require modifying vectors and gene delivery approaches to achieve effective results for cardiac gene therapy. Conclusion: In this book chapter, we integrate a historical perspective with recent advances that will likely affect clinical development in this research area.

scholarly journals Chitosan Applications Used in Medical Therapy of Tissue Regeneration

2016 ◽  
Vol 4 (2) ◽  
pp. 271 ◽  
Author(s):  
Alef Mustafa ◽  
Ana Maria Ionescu ◽  
Melat Cherim ◽  
Rodica Sîrbu
Keyword(s):  
Tissue Engineering ◽  
Tissue Regeneration ◽  
Biomedical Applications ◽  
Vascular Tissue ◽  
Bulk Material ◽  
Cell Types ◽  
Biological Molecules ◽  
Great Promise ◽  
Nucleus Pulposus Cells ◽  
Biological Specificity

Chitosan is an unique natural biopolymer that has great potential in tissue engineering applications and over the past several decades, it has emerged as a promising biomaterial for biomedical applications. Due to its various properties such as controllable biodegradability, biocompatibility, antimicrobial activity and functionalizability, chitosan can be used to form chitosan-based scaffolds and in different scaffold fabrication techniques. Over the years a great number of studies have been performed to evaluate the cytocompatibility of chitosan using a variety off cell types such as osteoblasts, chondrocytes, fibroblasts, nucleus pulposus cells, neutral and endothelial cells. It was shown that chitosan is biocompatible with these cell types and has the potential to be used for bone, cartilage, skin, intervertebral disc, ligament and tendon, and nerve and vascular tissue engineering. The flexibility of the processing conditions of chitosan aids in the fabrication of versatile substrates as scaffolds for tissue regeneration or carriers for biological molecules. It is critical to synthesize medical grade chitosan materials with controllable structure and properties that will allow the development of chitosan-based medical devices and it is beneficial to chemically design chitosan derivatives with molecular and biological specificity through bulk material modification. Despite all the challenges, chitosan holds great promise as a biomaterial for developing medical products and medical therapies.

scholarly journals Current Insights Into 3D Bioprinting: An Advanced Approach for Eye Tissue Regeneration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 308
Author(s):  
Sandra Ruiz-Alonso ◽  
Ilia Villate-Beitia ◽  
Idoia Gallego ◽  
Markel Lafuente-Merchan ◽  
Gustavo Puras ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Three Dimensional ◽  
Cell Types ◽  
Current Status ◽  
Great Promise ◽  
3D Bioprinting ◽  
Future Directions ◽  
Eye Tissues ◽  
Advanced Therapy ◽  
Different Cell Types

Three-dimensional (3D) printing is a game changer technology that holds great promise for a wide variety of biomedical applications, including ophthalmology. Through this emerging technique, specific eye tissues can be custom-fabricated in a flexible and automated way, incorporating different cell types and biomaterials in precise anatomical 3D geometries. However, and despite the great progress and possibilities generated in recent years, there are still challenges to overcome that jeopardize its clinical application in regular practice. The main goal of this review is to provide an in-depth understanding of the current status and implementation of 3D bioprinting technology in the ophthalmology field in order to manufacture relevant tissues such as cornea, retina and conjunctiva. Special attention is paid to the description of the most commonly employed bioprinting methods, and the most relevant eye tissue engineering studies performed by 3D bioprinting technology at preclinical level. In addition, other relevant issues related to use of 3D bioprinting for ocular drug delivery, as well as both ethical and regulatory aspects, are analyzed. Through this review, we aim to raise awareness among the research community and report recent advances and future directions in order to apply this advanced therapy in the eye tissue regeneration field.

scholarly journals Multiple Immediate-Early Gene-Deficient Herpes Simplex Virus Vectors Allowing Efficient Gene Delivery to Neurons in Culture and Widespread Gene Delivery to the Central Nervous System In Vivo

2001 ◽  
Vol 75 (9) ◽  
pp. 4343-4356 ◽  
Author(s):  
Caroline E. Lilley ◽  
Filitsa Groutsi ◽  
ZiQun Han ◽  
James A. Palmer ◽  
Patrick N. Anderson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Gene Delivery ◽  
Transgene Expression ◽  
Retrograde Transport ◽  
Spinal Ganglia ◽  
The Central Nervous System ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) has several potential advantages as a vector for delivering genes to the nervous system. The virus naturally infects and remains latent in neurons and has evolved the ability of highly efficient retrograde transport from the site of infection at the periphery to the site of latency in the spinal ganglia. HSV is a large virus, potentially allowing the insertion of multiple or very large transgenes. Furthermore, HSV does not integrate into the host chromosome, removing any potential for insertional activation or inactivation of cellular genes. However, the development of HSV vectors for the central nervous system that exploit these properties has been problematical. This has mainly been due to either vector toxicity or an inability to maintain transgene expression. Here we report the development of highly disabled versions of HSV-1 deleted for ICP27, ICP4, and ICP34.5/open reading frame P and with an inactivating mutation in VP16. These viruses express only minimal levels of any of the immediate-early genes in noncomplementing cells. Transgene expression is maintained for extended periods with promoter systems containing elements from the HSV latency-associated transcript promoter (J. A. Palmer et al., J. Virol. 74:5604–5618, 2000). Unlike less-disabled viruses, these vectors allow highly effective gene delivery both to neurons in culture and to the central nervous system in vivo. Gene delivery in vivo is further enhanced by the retrograde transport capabilities of HSV. Here the vector is efficiently transported from the site of inoculation to connected sites within the nervous system. This is demonstrated by gene delivery to both the striatum and substantia nigra following striatal inoculation; to the spinal cord, spinal ganglia, and brainstem following injection into the spinal cord; and to retinal ganglion neurons following injection into the superior colliculus and thalamus.

5. Reacting and thinking

2021 ◽  
pp. 76-88
Author(s):  
Jamie A. Davies
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Learning And Memory ◽  
Cell Types ◽  
The Body ◽  
The Central Nervous System ◽  
The Brain ◽  
Vast Network

This chapter assesses the nervous system. In the trunk of the body and the neck, the central nervous system (CNS) is called the spinal cord; in the head, it is called the brain. The CNS is dominated by two cell types: neurons and glia. The neurons form a vast network in which information is split, combined, and somehow processed. Examples of this processing include reflex arcs, the ‘circuitry’ that detects features such as edges in images coming from the eyes, and simple types of learning and memory. However, most other things in the brain, especially thinking and feeling, are not yet understood at all well.

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