The use of viral vectors to promote repair after spinal cord injury

Islam, Ashraful; Tom, Veronica J.

doi:10.1016/j.expneurol.2022.114102

Cited by 10 publications

(17 citation statements)

References 184 publications

(218 reference statements)

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“…54 Currently, no drugs or treatments can repair the damage caused by an SCI and restore function lost due to the injury, such as voluntary muscle movement and sensations. 57 Several drugs used in clinical trials for SCI were found to have low efficacy. Other medications have been demonstrated to merely treat postinjury symptoms, such as pain.…”

Section: Barriers Associated With Targeting Cnsmentioning

confidence: 99%

“…None have been shown to repair axons damaged by injury to restore function. 57 Drugs may also have off-target side effects. Using viral vectors to transmit genetic material is a prominent gene therapy strategy.…”

Section: Barriers Associated With Targeting Cnsmentioning

confidence: 99%

“…Other medications have been demonstrated to merely treat postinjury symptoms, such as pain. None have been shown to repair axons damaged by injury to restore function . Drugs may also have off-target side effects.…”

Section: Barriers Associated With Targeting Cnsmentioning

confidence: 99%

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Bioinspired Approaches for Central Nervous System Targeted Gene Delivery

Kumar,

Karim,

Sweety

et al. 2023

ACS Appl. Bio Mater.

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Disorders of the central nervous system (CNS) which include a wide range of neurodegenerative and neurological conditions have become a serious global issue. The presence of CNS barriers poses a significant challenge to the progress of designing effective therapeutic delivery systems, limiting the effectiveness of drugs, genes, and other therapeutic agents. Natural nanocarriers present in biological systems have inspired researchers to design unique delivery systems through biomimicry. As natural resource derived delivery systems are more biocompatible, current research has been focused on the development of delivery systems inspired by bacteria, viruses, fungi, and mammalian cells. Despite their structural potential and extensive physiological function, making them an excellent choice for biomaterial engineering, the delivery of nucleic acids remains challenging due to their instability in biological systems. Similarly, the efficient delivery of genetic material within the tissues of interest remains a hurdle due to a lack of selectivity and targeting ability. Considering that gene therapies are the holy grail for intervention in diseases, including neurodegenerative disorders such as Alzheimer's disease, Parkinson's Disease, and Huntington's disease, this review centers around recent advances in bioinspired approaches to gene delivery for the prevention of CNS disorders.

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Section: Barriers Associated With Targeting Cnsmentioning

confidence: 99%

Section: Barriers Associated With Targeting Cnsmentioning

confidence: 99%

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Bioinspired Approaches for Central Nervous System Targeted Gene Delivery

Kumar,

Karim,

Sweety

et al. 2023

ACS Appl. Bio Mater.

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“…The most commonly used genetic cargo carriers to enable gene delivery are viral vectors usually derived from the capsid components and include adenovirus (AV), lentivirus, and adeno‐associated virus (AAV). [ 25 ] Once delivered to their target cell, viral vectors enable efficient delivery and often sustained expression of genetic material encoding large macromolecules. For example, ChABC enzyme has a short half‐life and rapidly degrades in the lesion site, [14a−c] but local delivery of ChABC pDNA using a lentiviral vector overcomes this issue and generates immunoprotective effects in a rat model of acute SCI [14d]…”

Section: Scimentioning

confidence: 99%

“…[ 27 ] For spinal cord applications, viral vectors have been extensively used in preclinical studies as part of multifaceted strategies to treat cord injury but have not yet been brought to clinical trials. [ 25 ] Anderson et al used local AAV delivery of plasmid DNA through injection of gene‐activated hydrogel deposits to drive expression of several key signaling molecules around the injury site (insulin‐like growth factor 1, osteopontin, and ciliary‐derived neurotrophic factor) to reactivate the intrinsic growth potential of adult spinal cord neurons—propelling axonal growth through the injury site. [ 28 ] Other studies have successfully upregulated neurotrophic factor (e.g., nerve growth factor) expression, immunocytokine expression (e.g., IL‐10, IL‐4), and silenced detrimental gene expression using short hairpin RNA (shRNA) as part of scaffold‐implant mediated delivery systems.…”

Section: Scimentioning

confidence: 99%

Biomaterial‐Based Gene Delivery to Central Nervous System Cells for the Treatment of Spinal Cord Injury

McGuire,

Stasiewicz,

Woods

et al. 2023

Advanced NanoBiomed Research

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Spinal cord injury (SCI) is a devastating traumatic injury often causing permanent loss of function. The challenge of treating SCI stems from the development of a complex pathophysiology at the site of injury, involving multiple biochemical cascades, widespread inflammation, blood supply interruption, inhibitory scar formation, and poor regrowth of injured axons. Clinical options are limited to surgical stabilization and attempt to ameliorate secondary damage following injury. Gene therapy has significant potential to tackle multiple aspects of SCI and improve functional outcomes. The emergence of a diverse array of biomaterial‐based nonviral nanoparticle vectors capable of delivering gene‐modifying nucleic acids offers the potential to improve the efficiency and specificity of genetic cargos for spinal cord regeneration. In this review, the progress that has been made in the field of SCI repair and the different types of nanoparticles and nucleic acid cargoes that have been used are outlined, placing a particular focus on the different cell types and pathways targeted. While many challenges remain, a perspective on the future of the field of nanoparticle‐mediated gene delivery for SCI is provided, including using biomaterial scaffolds engineered specifically for SCI to deliver gene therapeutics and the exciting opportunities that exist in the post‐COVID landscape.

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