scholarly journals Adeno-associated virus (AAV) reduces cortical dendritic complexity in a TLR9-dependent manner

2021 ◽  
Author(s):  
Christos M. Suriano ◽  
Jessica L. Verpeut ◽  
Neerav Kumar ◽  
Jie Ma ◽  
Caroline Jung ◽  
...  
Keyword(s):  
Nervous System ◽  
Gene Delivery ◽  
Dependent Manner ◽  
Neuronal Structure ◽  
Adeno Associated Virus ◽  
Gene Therapies ◽  
Efficient Gene ◽  
Core Feature ◽  
And Function ◽  
Dendritic Complexity

Recombinant adeno-associated viruses (AAVs) allow rapid and efficient gene delivery in the nervous system. AAVs are widely used in research and are the basis of multiple FDA-approved gene therapies. Here, we find that the immune response to AAV's genome reduces dendritic complexity in mammalian cortex. Dendritic loss associated with AAV-mediated gene delivery occurs at experimentally-relevant titers, cannot be explained by responses to transgene expression or surgery, and is not restricted to a particular capsid serotype, encoded transgene, promoter, or production facility. AAV-associated dendritic loss is accompanied by a decrease in the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) and upregulation of immune molecules that can limit dendritic complexity and synaptic transmission. Blocking detection of unmethylated CpG-rich DNA via Toll-like receptor 9 (TLR9) protects dendritic complexity, suggesting that immunodetection of a core feature of the AAV genome triggers dendritic loss. These results reveal previously unsuspected impacts of AAV on neuronal structure and function and identify TLR9 inhibitors as important tools to improve the safety and efficacy of AAV-mediated gene delivery in the nervous system.

scholarly journals Carbon Dot Nanoparticles: Exploring the Potential Use for Gene Delivery in Ophthalmic Diseases

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 935
Author(s):  
Manas R. Biswal ◽  
Sofia Bhatia
Keyword(s):  
Gene Delivery ◽  
Therapeutic Option ◽  
Retinal Dystrophy ◽  
Retinal Cells ◽  
Adeno Associated Virus ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Efficient Gene ◽  
New Type ◽  
Viral Nanoparticles

Ocular gene therapy offers significant potential for preventing retinal dystrophy in patients with inherited retinal dystrophies (IRD). Adeno-associated virus (AAV) based gene transfer is the most common and successful gene delivery approach to the eye. These days, many studies are using non-viral nanoparticles (NPs) as an alternative therapeutic option because of their unique properties and biocompatibility. Here, we discuss the potential of carbon dots (CDs), a new type of nanocarrier for gene delivery to the retinal cells. The unique physicochemical properties of CDs (such as optical, electronic, and catalytic) make them suitable for biosensing, imaging, drug, and gene delivery applications. Efficient gene delivery to the retinal cells using CDs depends on various factors, such as photoluminescence, quantum yield, biocompatibility, size, and shape. In this review, we focused on different approaches used to synthesize CDs, classify CDs, various pathways for the intake of gene-loaded carbon nanoparticles inside the cell, and multiple studies that worked on transferring nucleic acid in the eye using CDs.

scholarly journals Review on various factors responsible for neurodegenerative disorders

2021 ◽  
Vol 16 (1) ◽  
pp. 126-132
Author(s):  
Harshwardhan J Tembhurnikar ◽  
Neha D Thool ◽  
Rasika J Patil ◽  
Ranjita K Das
Keyword(s):  
Oxidative Stress ◽  
Nervous System ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Critical Role ◽  
Structure And Function ◽  
Neuronal Structure ◽  
Pathophysiological Mechanisms ◽  
Neurological Illnesses ◽  
And Function

Neurodegenerative disorders are nervous system disorders that result in the loss of neuronal structure and function. As shown in Alzheimer's and Parkinson's disease, these changes cause a loss of various capacities, including cognition and mobility. Several factors have been discovered to play a critical role in the etiology of common neurological illnesses, including oxidative stress and protein misfolding. It's still unclear if these factors cause or contribute to the progression of the illnesses. Despite efforts to understand the molecular and pathophysiological mechanisms behind these pathways, many aspects remain unknown. The goal of this review is to investigate the numerous factors linked to neurodegeneration.

Neuronal growth and target recognition: lessons from the leech

2001 ◽  
Vol 79 (2) ◽  
pp. 204-217 ◽  
Author(s):  
Michael W Baker ◽  
Eduardo R Macagno
Keyword(s):  
Nervous System ◽  
Target Recognition ◽  
Structure And Function ◽  
Neuronal Structure ◽  
Peripheral Neurons ◽  
Unique System ◽  
Molecular Studies ◽  
The Subject ◽  
The 1960S ◽  
And Function

The nervous system of the leech has been the subject of numerous studies since its "rediscovery" in the 1960s as a unique system for the study of the properties of glial cells. Subsequently, anatomical, physiological, and embryological studies of identified neurons have yielded a wealth of information about the differentiation of neuronal structure and function. In recent years, cellular approaches to the development of identified central and peripheral neurons have been complemented by molecular studies that promise to reveal the mechanisms by which neurons form their complex arbors and innervate specific targets.

scholarly journals A developmental framework linking neurogenesis and circuit formation in the Drosophila CNS

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Brandon Mark ◽  
Sen-Lin Lai ◽  
Aref Arzan Zarin ◽  
Laurina Manning ◽  
Heather Q Pollington ◽  
...  
Keyword(s):  
Nervous System ◽  
Neural Circuit ◽  
Neural Progenitors ◽  
Dependent Manner ◽  
Neuronal Diversity ◽  
Synaptic Targeting ◽  
Connectivity Structure ◽  
Temporal Identity ◽  
And Function ◽  
Circuit Formation

The mechanisms specifying neuronal diversity are well-characterized, yet it remains unclear how or if these mechanisms regulate neural circuit assembly. To address this, we mapped the developmental origin of 160 interneurons from seven bilateral neural progenitors (neuroblasts), and identify them in a synapse-scale TEM reconstruction of the Drosophila larval CNS. We find that lineages concurrently build the sensory and motor neuropils by generating sensory and motor hemilineages in a Notch-dependent manner. Neurons in a hemilineage share common synaptic targeting within the neuropil, which is further refined based on neuronal temporal identity. Connectome analysis shows that hemilineage-temporal cohorts share common connectivity. Finally, we show that proximity alone cannot explain the observed connectivity structure, suggesting hemilineage/temporal identity confers an added layer of specificity. Thus, we demonstrate that the mechanisms specifying neuronal diversity also govern circuit formation and function, and that these principles are broadly applicable throughout the nervous system.

scholarly journals 567. Adeno-Associated Virus Vector 8 (AAV8) Provides Efficient Gene Delivery to Skeletal Muscles In Utero by Systemic Adminstration

2006 ◽  
Vol 13 ◽  
pp. S218
Author(s):  
Bhanu Munil Koppanati ◽  
Juan Li ◽  
Bing Wang ◽  
Xiao Xiao ◽  
Paula Ruth Clemens
Keyword(s):  
Gene Delivery ◽  
Skeletal Muscles ◽  
In Utero ◽  
Virus Vector ◽  
Adeno Associated Virus ◽  
Efficient Gene

scholarly journals Development and Optimization of Herpes Simplex Virus Vectors for Multiple Long-Term Gene Delivery to the Peripheral Nervous System

2000 ◽  
Vol 74 (12) ◽  
pp. 5604-5618 ◽  
Author(s):  
J. A. Palmer ◽  
R. H. Branston ◽  
C. E. Lilley ◽  
M. J. Robinson ◽  
F. Groutsi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Gene Delivery ◽  
Active Region ◽  
Spinal Ganglia ◽  
Efficient Gene ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) has often been suggested as a suitable vector for gene delivery to the peripheral nervous system as it naturally infects sensory nerve terminals before retrograde transport to the cell body in the spinal ganglia where latency is established. HSV vectors might therefore be particularly appropriate for the study and treatment of chronic pain following vector administration by relatively noninvasive peripheral routes. However parameters allowing safe and efficient gene delivery to spinal ganglia following peripheral vector inoculation, or the long-term expression of delivered genes, have not been comprehensively studied. We have identified combinations of deletions from the HSV genome which allow highly efficient gene delivery to spinal dorsal root ganglia (DRGs) following either footpad or sciatic nerve injection. These vectors have ICP34.5 deleted and have inactivating mutations in vmw65. We also report that peripheral replication is probably necessary for the efficient establishment of latency in vivo, as fully replication-incompetent HSV vectors allow efficient gene expression in DRGs only after peripheral inoculation at a high virus dose. Very low transduction efficiencies are otherwise achieved. In parallel, promoters have been developed that allow the long-term expression of individual or pairs of genes in DRGs by using elements from the latently active region of the virus to confer a long-term activity onto a number of promoters which otherwise function only in the short term. This work further defines elements and mechanisms within the latently active region that are necessary for long-term gene expression and for the first time allows multiple inserted genes to be expressed from HSV vectors during latency.

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