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Nonviral Vectors for Gene Delivery.

Baoum, Abdulgader Ahmed.

Nonviral Vectors for Gene Delivery.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Nonviral Vectors for Gene Delivery.
作者:	Baoum, Abdulgader Ahmed.
面頁冊數:	235 p.
附註:	Source: Dissertation Abstracts International, Volume: 72-07, Section: B, page: .
附註:	Adviser: Cory J. Berkland.
Contained By:	Dissertation Abstracts International72-07B.
標題:	Biology, Genetics.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3453562
ISBN:	9781124616902

Nonviral Vectors for Gene Delivery.
Baoum, Abdulgader Ahmed.

Nonviral Vectors for Gene Delivery. - 235 p.

Source: Dissertation Abstracts International, Volume: 72-07, Section: B, page: .

Thesis (Ph.D.)--University of Kansas, 2011.

The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells.

ISBN: 9781124616902Subjects--Topical Terms:

226893
Biology, Genetics.

Nonviral Vectors for Gene Delivery.
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245 1 0 $a Nonviral Vectors for Gene Delivery.
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500 $a Source: Dissertation Abstracts International, Volume: 72-07, Section: B, page: .
500 $a Adviser: Cory J. Berkland.
502 $a Thesis (Ph.D.)--University of Kansas, 2011.
520 $a The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells.
520 $a PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (&sim;200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium.
520 $a On the other hand, a more simple method to synthesize 50-200 nm complexes capable of high transfection efficiency or high gene knockdown was also explored. Positively charged CPPs were complexed with pDNA or siRNA, which resulted in 'loose' (&sim;1 micron) particles. These were then condensed into small nanoparticles by using calcium, which formed "soft" crosslinks by interacting with both phosphates on nucleic acids and amines on CPPs. An optimal amount of CaCl2 produced stable, &sim;100 nm complexes that exhibited higher transfection efficiency and gene silencing than PEI polyplexes. CPPs also displayed negligible cytotoxicity up to 5 mg/mL. Biophysical studies of the pDNA structure within complexes suggested that pDNA within CPP complexes (condensed with calcium) had similar structure, but enhanced thermal stability compared to PEI complexes. Thus, CPP complexes emerged as simple, attractive candidates for future studies on nonviral gene delivery in vivo.
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