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Intracellular considerations in the ...

Mishra, Swaroop.

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Intracellular considerations in the development of non-viral nucleic acid delivery systems for systemic administration.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Intracellular considerations in the development of non-viral nucleic acid delivery systems for systemic administration./
Author:	Mishra, Swaroop.
Description:	203 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-12, Section: B, page: 6374.
Contained By:	Dissertation Abstracts International66-12B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3197323
ISBN:	9780542428043

Intracellular considerations in the development of non-viral nucleic acid delivery systems for systemic administration.
Mishra, Swaroop.

Intracellular considerations in the development of non-viral nucleic acid delivery systems for systemic administration. - 203 p.

Source: Dissertation Abstracts International, Volume: 66-12, Section: B, page: 6374.

Thesis (Ph.D.)--California Institute of Technology, 2006.

Non-viral nucleic acid delivery systems must condense nucleic acids into small particles, confer protection from degrading factors in serum and in cells, achieve uptake to targeted cells, direct nucleic acids to appropriate intracellular destinations, release this cargo to permit its action, and exhibit minimal toxicity. The nature of synthetic vectors allows for facile addition of new features, but these modifications can affect performance in unanticipated ways. The effective combination of functional components necessitates a systems approach, where the materials design simultaneously considers the functional environment of and the various barriers to delivery. This thesis facilitates and promotes a systems approach by undertaking development of an improved mechanistic understanding of non-viral gene transfer in vitro, emphasizing elucidation of delivery vehicles' interactions with and behavior within cells. Special attention is given to the gene delivery behavior of cyclodextrin-containing polycations.

ISBN: 9780542428043Subjects--Topical Terms:

1017686
Biology, Cell.

Intracellular considerations in the development of non-viral nucleic acid delivery systems for systemic administration.
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100 1 $a Mishra, Swaroop. $3 1913424
245 1 0 $a Intracellular considerations in the development of non-viral nucleic acid delivery systems for systemic administration.
300 $a 203 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-12, Section: B, page: 6374.
500 $a Adviser: Mark E. Davis.
502 $a Thesis (Ph.D.)--California Institute of Technology, 2006.
520 $a Non-viral nucleic acid delivery systems must condense nucleic acids into small particles, confer protection from degrading factors in serum and in cells, achieve uptake to targeted cells, direct nucleic acids to appropriate intracellular destinations, release this cargo to permit its action, and exhibit minimal toxicity. The nature of synthetic vectors allows for facile addition of new features, but these modifications can affect performance in unanticipated ways. The effective combination of functional components necessitates a systems approach, where the materials design simultaneously considers the functional environment of and the various barriers to delivery. This thesis facilitates and promotes a systems approach by undertaking development of an improved mechanistic understanding of non-viral gene transfer in vitro, emphasizing elucidation of delivery vehicles' interactions with and behavior within cells. Special attention is given to the gene delivery behavior of cyclodextrin-containing polycations.
520 $a Simple modifications to delivery systems can have unanticipated consequences. In Chapter 2, it is shown that greater distance between toxicity-reducing cyclodextrin moieties and amidine charge centers increases both the transfection efficiency and toxicity of a polycationic vector. Chapter 3 shows data demonstrating that modification with poly(ethylene glycol) for extracellular salt-stabilization alters non-viral gene delivery particles' intracellular trafficking and resulting gene expression. Taken together, the results reveal that non-viral gene delivery vehicles behave as assembled, multifunctional systems.
520 $a pH-buffering components exhibit complex behavior in non-viral gene delivery. In Chapter 4, the intracellular activity of such components is quantified using confocal microscopy. Analysis of chloroquine and its chemical analogues demonstrates in Chapter 5 that chloroquine improves non-viral gene transfer through pH-buffering as well as through enhanced nucleic acid unpackaging and its own interactions with nucleic acids. Chapter 6 gives results that characterize delivery behavior of analogous vectors with and without pH-buffering capacity and show that factors beyond buffering activity contribute to improved transfection efficiency. Collectively, these results emphasize consideration of new system components' effects on all functions of a non-viral gene delivery system.
520 $a A systems approach requires comprehensive consideration of the gene delivery process. Chapter 7 reviews current understanding of intracellular barriers to non-viral gene delivery, and Chapter 8 offers recommendations for future work.
590 $a School code: 0037.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Molecular. $3 1017719
690 $a 0379
690 $a 0369
690 $a 0307
710 2 0 $a California Institute of Technology. $3 726902
773 0 $t Dissertation Abstracts International $g 66-12B.
790 1 0 $a Davis, Mark E., $e advisor
790 $a 0037
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3197323