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Gene therapy approaches for spinal c...

Bright, Corinne.

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Gene therapy approaches for spinal cord injury.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Gene therapy approaches for spinal cord injury./
Author:	Bright, Corinne.
Description:	296 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-11, Section: B, page: 5858.
Contained By:	Dissertation Abstracts International65-11B.
Subject:	Engineering, Biomedical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3155597
ISBN:	0496163175

Gene therapy approaches for spinal cord injury.
Bright, Corinne.

Gene therapy approaches for spinal cord injury. - 296 p.

Source: Dissertation Abstracts International, Volume: 65-11, Section: B, page: 5858.

Thesis (Ph.D.)--The Johns Hopkins University, 2005.

As the biomedical engineering field expands, combination technologies are demonstrating enormous potential for treating human disease. In particular, intersections between the rapidly developing fields of gene therapy and tissue engineering hold promise to achieve tissue regeneration. Nonviral gene therapy uses plasmid DNA to deliver therapeutic proteins in vivo for extended periods of time. Tissue engineering employs biomedical materials, such as polymers, to support the regrowth of injured tissue. In this thesis, a combination strategy to deliver genes and drugs in a polymeric scaffold was applied to a spinal cord injury model.

ISBN: 0496163175Subjects--Topical Terms:

1017684
Engineering, Biomedical.

Gene therapy approaches for spinal cord injury.
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100 1 $a Bright, Corinne. $3 1938412
245 1 0 $a Gene therapy approaches for spinal cord injury.
300 $a 296 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-11, Section: B, page: 5858.
500 $a Adviser: Kam W. Leong.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2005.
520 $a As the biomedical engineering field expands, combination technologies are demonstrating enormous potential for treating human disease. In particular, intersections between the rapidly developing fields of gene therapy and tissue engineering hold promise to achieve tissue regeneration. Nonviral gene therapy uses plasmid DNA to deliver therapeutic proteins in vivo for extended periods of time. Tissue engineering employs biomedical materials, such as polymers, to support the regrowth of injured tissue. In this thesis, a combination strategy to deliver genes and drugs in a polymeric scaffold was applied to a spinal cord injury model.
520 $a In order to develop a platform technology to treat spinal cord injury, several nonviral gene delivery systems and polymeric scaffolds were evaluated in vitro and in vivo. Nonviral vector trafficking was evaluated in primary neuronal culture to develop an understanding of the barriers to gene transfer in neurons and their supporting glia. Although the most efficient gene carrier in vitro differed from the optimal gene carrier in vivo, confocal and electron microscopy of these nonviral vectors provided insights into the interaction of these vectors with the nucleus. A novel pathway for delivering nanoparticles into the nuclei of neurons and Schwann cells via vesicle trafficking was observed in this study. Reporter gene expression levels were evaluated after direct and remote delivery to the spinal cord, and the optimal nonviral vector, dose, and delivery strategy were applied to deliver the gene encoding the basic fibroblast growth factor (bFGF) to the spinal cord. An injectable and biocompatible gel, composed of the amphiphillic polymer poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) was evaluated as a drug and gene delivery system in vitro, and combined with the optimized nonviral gene delivery system to treat spinal cord injury. Plasmid DNA encoding the bFGF gene and the therapeutic NEP1--40 peptide were incorporated in the PEG-PCL-PEG gel and injected into a lesion transecting the main dorsomedial and minor ventral medial corticospinal tract (CST). The degree of collateralization of the transected CST was quantified as an indicator of the regenerative potential of these treatments. At one month post-injury, we observed the robust rostral collateralization of the CST tract in response to the bFGF plasmid-loaded gel. In conclusion, we hope that this platform technology can be applied to the sustained local delivery of other proteins for the treatment of spinal cord injury.
590 $a School code: 0098.
650 4 $a Engineering, Biomedical. $3 1017684
650 4 $a Chemistry, Polymer. $3 1018428
650 4 $a Engineering, Materials Science. $3 1017759
690 $a 0541
690 $a 0495
690 $a 0794
710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 65-11B.
790 1 0 $a Leong, Kam W., $e advisor
790 $a 0098
791 $a Ph.D.
792 $a 2005
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3155597