Advances in Engineering HSV Vectors for Gene Transfer to the Nervous System

2003 ◽  
pp. 127-163 ◽  
Author(s):  
M. Karina Soares ◽  
William F. Goins ◽  
Joseph C. Glorioso ◽  
David J. Fink
Keyword(s):  
Nervous System ◽  
Gene Transfer

Extensiveβ-Glucuronidase Activity in Murine Central Nervous System after Adenovirus-Mediated Gene Transfer to Brain

1998 ◽  
Vol 9 (16) ◽  
pp. 2331-2340 ◽  
Author(s):  
Abdi Ghodsi ◽  
Colleen Stein ◽  
Todd Derksen ◽  
Gongyu Yang ◽  
Richard D. Anderson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gene Transfer ◽  
Glucuronidase Activity

Gene Transfer into the Nervous System using Recombinant Herpes Virus Vectors

1992 ◽  
pp. 118-132 ◽  
Author(s):  
X. O. Breakefield ◽  
Q. Huang ◽  
J. K. Andersen ◽  
M. F. Kramer ◽  
W. R. Bebrin ◽  
...  
Keyword(s):  
Nervous System ◽  
Gene Transfer ◽  
Herpes Virus ◽  
Virus Vectors ◽  
Herpès Virus

Viral Vector-Mediated Gene Transfer in the Nervous System

Viral Vectors ◽  
1995 ◽  
pp. 119-132 ◽  
Author(s):  
J. Verhaagen ◽  
W.T.J.M.C. Hermens ◽  
A.J.G.D. Holtmaat ◽  
A.B. Oestreicher ◽  
W.H. Gispen ◽  
...  
Keyword(s):  
Nervous System ◽  
Gene Transfer ◽  
Viral Vector

scholarly journals Methods for Gene Transfer to the Central Nervous System

2014 ◽  
pp. 125-197 ◽  
Author(s):  
Boris Kantor ◽  
Rachel M. Bailey ◽  
Keon Wimberly ◽  
Sahana N. Kalburgi ◽  
Steven J. Gray
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gene Transfer ◽  
The Central Nervous System

scholarly journals Gene Transfer in Rodent Nervous Tissue Following Hindlimb Intramuscular Delivery of Recombinant Adeno-Associated Virus Serotypes AAV2/6, AAV2/8, and AAV2/9

2019 ◽  
Vol 14 ◽  
pp. 117906951988902 ◽  
Author(s):  
Asad Jan ◽  
Mette Richner ◽  
Christian B Vægter ◽  
Jens R Nyengaard ◽  
Poul H Jensen
Keyword(s):  
Nervous System ◽  
Viral Load ◽  
Green Fluorescent Protein ◽  
Gene Transfer ◽  
Enhanced Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Adeno Associated Virus ◽  
Green Fluorescent ◽  
Virus Delivery ◽  
Intramuscular Delivery

Recombinant adeno-associated virus (rAAV) vectors have emerged as the safe vehicles of choice for long-term gene transfer in mammalian nervous system. Recombinant adeno-associated virus–mediated localized gene transfer in adult nervous system following direct inoculation, that is, intracerebral or intrathecal, is well documented. However, recombinant adeno-associated virus delivery in defined neuronal populations in adult animals using less-invasive methods as well as avoiding ectopic gene expression following systemic inoculation remain challenging. Harnessing the capability of some recombinant adeno-associated virus serotypes for retrograde transduction may potentially address such limitations (Note: The term retrograde transduction in this manuscript refers to the uptake of injected recombinant adeno-associated virus particles at nerve terminals, retrograde transport, and subsequent transduction of nerve cell soma). In some studies, recombinant adeno-associated virus serotypes 2/6, 2/8, and 2/9 have been shown to exhibit transduction of connected neuroanatomical tracts in adult animals following lower limb intramuscular recombinant adeno-associated virus delivery in a pattern suggestive of retrograde transduction. However, an extensive side-by-side comparison of these serotypes following intramuscular delivery regarding tissue viral load, and the effect of promoter on transgene expression, has not been performed. Hence, we delivered recombinant adeno-associated virus serotypes 2/6, 2/8, or 2/9 encoding enhanced green fluorescent protein (eGFP), under the control of either cytomegalovirus (CMV) or human synapsin (hSyn) promoter, via a single unilateral hindlimb intramuscular injection in the bicep femoris of adult C57BL/6J mice. Four weeks post injection, we quantified viral load and transgene (enhanced green fluorescent protein) expression in muscle and related nervous tissues. Our data show that the select recombinant adeno-associated virus serotypes transduce sciatic nerve and groups of neurons in the dorsal root ganglia on the injected side, indicating that the intramuscular recombinant adeno-associated virus delivery is useful for achieving gene transfer in local neuroanatomical tracts. We also observed sparse recombinant adeno-associated virus viral delivery or eGFP transduction in lumbar spinal cord and a noticeable lack thereof in brain. Therefore, further improvements in recombinant adeno-associated virus design are warranted to achieve efficient widespread retrograde transduction following intramuscular and possibly other peripheral routes of delivery.

scholarly journals Pharmacological, Cell, and Gene Therapy Strategies to Promote Spinal Cord Regeneration

2002 ◽  
Vol 11 (6) ◽  
pp. 593-613 ◽  
Author(s):  
Bas Blits ◽  
Gerard J. Boer ◽  
Joost Verhaagen
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Nervous System ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Cell Transplantation ◽  
Ex Vivo ◽  
Neuronal Survival ◽  
Genetically Modified ◽  
Injured Spinal Cord

In this review, recent studies using pharmacological treatment, cell transplantation, and gene therapy to promote regeneration of the injured spinal cord in animal models will be summarized. Pharmacological and cell transplantation treatments generally revealed some degree of effect on the regeneration of the injured ascending and descending tracts, but further improvements to achieve a more significant functional recovery are necessary. The use of gene therapy to promote repair of the injured nervous system is a relatively new concept. It is based on the development of methods for delivering therapeutic genes to neurons, glia cells, or nonneural cells. Direct in vivo gene transfer or gene transfer in combination with (neuro)transplantation (ex vivo gene transfer) appeared powerful strategies to promote neuronal survival and axonal regrowth following traumatic injury to the central nervous system. Recent advances in understanding the cellular and molecular mechanisms that govern neuronal survival and neurite outgrowth have enabled the design of experiments aimed at viral vector-mediated transfer of genes encoding neurotrophic factors, growth-associated proteins, cell adhesion molecules, and antiapoptotic genes. Central to the success of these approaches was the development of efficient, nontoxic vectors for gene delivery and the acquirement of the appropriate (genetically modified) cells for neurotransplantation. Direct gene transfer in the nervous system was first achieved with herpes viral and E1-deleted adenoviral vectors. Both vector systems are problematic in that these vectors elicit immunogenic and cytotoxic responses. Adeno-associated viral vectors and lentiviral vectors constitute improved gene delivery systems and are beginning to be applied in neuroregeneration research of the spinal cord. Ex vivo approaches were initially based on the implantation of genetically modified fibroblasts. More recently, transduced Schwann cells, genetically modified pieces of peripheral nerve, and olfactory ensheathing glia have been used as implants into the injured spinal cord.

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