scholarly journals Prolonged Transgene Expression Mediated by a Helper-Dependent Adenoviral Vector (hdAd) in the Central Nervous System

2000 ◽  
Vol 2 (2) ◽  
pp. 105-113 ◽  
Author(s):  
Linglong Zou ◽  
Heshan Zhou ◽  
Lucio Pastore ◽  
Keyi Yang
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jerusha Naidoo ◽  
Deborah Young

Substantial progress has been made in the development of novel gene therapy strategies for central nervous system (CNS) disorders in recent years. However, unregulated transgene expression is a significant issue limiting human applications due to the potential side effects from excessive levels of transgenic protein that indiscriminately affect both diseased and nondiseased cells. Gene regulation systems are a tool by which tight tissue-specific and temporal regulation of transgene expression may be achieved. This review covers the features of ideal regulatory systems and summarises the mechanics of current exogenous and endogenous gene regulation systems and their utility in the CNS.


2009 ◽  
Vol 17 (4) ◽  
pp. 641-650 ◽  
Author(s):  
David M Yurek ◽  
Anita M Fletcher ◽  
George M Smith ◽  
Kim B Seroogy ◽  
Assem G Ziady ◽  
...  

2001 ◽  
Vol 75 (9) ◽  
pp. 4343-4356 ◽  
Author(s):  
Caroline E. Lilley ◽  
Filitsa Groutsi ◽  
ZiQun Han ◽  
James A. Palmer ◽  
Patrick N. Anderson ◽  
...  

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.


Development ◽  
1999 ◽  
Vol 126 (11) ◽  
pp. 2475-2481 ◽  
Author(s):  
R. Battye ◽  
A. Stevens ◽  
J.R. Jacobs

Guidance of axons towards or away from the midline of the central nervous system during Drosophila embryogenesis reflects a balance of attractive and repulsive cues originating from the midline. Here we demonstrate that Slit, a protein secreted by the midline glial cells provides a repulsive cue for the growth cones of axons and muscle cells. Embryos lacking slit function show a medial collapse of lateral axon tracts and ectopic midline crossing of ventral muscles. Transgene expression of slit in the midline restores axon patterning. Ectopic expression of slit inhibits formation of axon tracts at locations of high Slit production and misdirects axon tracts towards the midline. slit interacts genetically with roundabout, which encodes a putative receptor for growth cone repulsion.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Gianluca Verlengia ◽  
Yoshitaka Miyagawa ◽  
Selene Ingusci ◽  
Justus B. Cohen ◽  
Michele Simonato ◽  
...  

1993 ◽  
Vol 3 (3) ◽  
pp. 219-223 ◽  
Author(s):  
Beverly L. Davidson ◽  
Edward D. Allen ◽  
Karen F. Kozarsky ◽  
James M. Wilson ◽  
Blake J. Roessler

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