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Molecular mechanisms in lipid-based ...

Ahmad, Ayesha.

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Molecular mechanisms in lipid-based gene delivery systems.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Molecular mechanisms in lipid-based gene delivery systems./
Author:	Ahmad, Ayesha.
Description:	204 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0116.
Contained By:	Dissertation Abstracts International65-01B.
Subject:	Biophysics, General. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3120346

Molecular mechanisms in lipid-based gene delivery systems.
Ahmad, Ayesha.

Molecular mechanisms in lipid-based gene delivery systems. - 204 p.

Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0116.

Thesis (Ph.D.)--University of California, Santa Barbara, 2004.

Lipid-mediated delivery is the prevalent choice for synthetic carriers of DNA for application to gene therapy. Recent setbacks in the use of these vectors as gene delivery agents have prompted a re-evaluation of design and functionality of these systems. Identification of the effects of certain physical properties of the lipid carriers have on the transfection efficiency (TE) is essential in developing viable carriers. Through x-ray diffraction, we have examined cationic lipid-DNA (CL-DNA) complexes that self-assemble into two main structures, lamellar, LCa , or inverted hexagonal complexes, HCII . Interactions between the CL-DNA complexes, which adopt the different structures, and the plasma membrane of cells have been analyzed, with respect to the TE of the complexes. For HCII complexes, the TE remains at a constant high level, which is attributed to its fusogenic properties. For LCa complexes, TE, follows are gaussian curve, with an exponential decrease in efficiency that is governed by membrane charge density, sigma M, and membrane bending rigidity, kappa.Subjects--Topical Terms:

1019105
Biophysics, General.

Molecular mechanisms in lipid-based gene delivery systems.
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100 1 $a Ahmad, Ayesha. $3 1952502
245 1 0 $a Molecular mechanisms in lipid-based gene delivery systems.
300 $a 204 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0116.
500 $a Chair: Cyrus R. Safinya.
502 $a Thesis (Ph.D.)--University of California, Santa Barbara, 2004.
520 $a Lipid-mediated delivery is the prevalent choice for synthetic carriers of DNA for application to gene therapy. Recent setbacks in the use of these vectors as gene delivery agents have prompted a re-evaluation of design and functionality of these systems. Identification of the effects of certain physical properties of the lipid carriers have on the transfection efficiency (TE) is essential in developing viable carriers. Through x-ray diffraction, we have examined cationic lipid-DNA (CL-DNA) complexes that self-assemble into two main structures, lamellar, LCa , or inverted hexagonal complexes, HCII . Interactions between the CL-DNA complexes, which adopt the different structures, and the plasma membrane of cells have been analyzed, with respect to the TE of the complexes. For HCII complexes, the TE remains at a constant high level, which is attributed to its fusogenic properties. For LCa complexes, TE, follows are gaussian curve, with an exponential decrease in efficiency that is governed by membrane charge density, sigma M, and membrane bending rigidity, kappa.
520 $a Altering certain physical properties of the lipids, including head-group size and charge and chain saturation, we examine the behavior of these complexes as gene delivery agents. Transfection efficiency plots for complexes containing monovalent or multivalent lipids mixed with the neutral lipid (NL) DOPC, at various CL/NL ratios, merge on to a universal TE curve when plotted as a function of membrane charge density. This universal TE curve identifies three regimes of interest, low, intermediate, and high sigmaM, that can be attributed to different interactions in the DNA delivery process. We find that the bending rigidity also alters the behavior of the CL-DNA complexes, but it only dominates the interactions at low sigmaM. Altering these two physical parameters, complexes exhibiting LCa structure can be optimized to rival other highly transfectant lipid systems, including inverted hexagonal ( HCII ) DOTAP/DOPE complexes. Systematic changes allow identification of key attributes of complexes that will allow for the rational design of lipid-based delivery systems.
590 $a School code: 0035.
650 4 $a Biophysics, General. $3 1019105
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710 2 0 $a University of California, Santa Barbara. $3 1017586
773 0 $t Dissertation Abstracts International $g 65-01B.
790 1 0 $a Safinya, Cyrus R., $e advisor
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791 $a Ph.D.
792 $a 2004
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