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Investigation and Manipulation of th...

Briley, William Edward.

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Investigation and Manipulation of the Local Microenvironment of Spherical Nucleic Acid Nanoconjugates.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Investigation and Manipulation of the Local Microenvironment of Spherical Nucleic Acid Nanoconjugates./
作者:	Briley, William Edward.
面頁冊數:	133 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-10(E), Section: B.
Contained By:	Dissertation Abstracts International77-10B(E).
標題:	Nanotechnology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10117274
ISBN:	9781339786773

Investigation and Manipulation of the Local Microenvironment of Spherical Nucleic Acid Nanoconjugates.
Briley, William Edward.

Investigation and Manipulation of the Local Microenvironment of Spherical Nucleic Acid Nanoconjugates. - 133 p.

Source: Dissertation Abstracts International, Volume: 77-10(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2016.

For the past several decades, tremendous efforts have been made by many to battle cancer,one of the leading causes of death in the United States and around the world. Unfortunately, the diagnosis and treatment of many genetically-based disorders such as cancer remains very difficult to this day. This is due to the fact that current technologies are unable to adequately differentiate between healthy and diseased cells. In many cases, state-of-the-art diagnostic and therapeutics for genetic disorders rely on targeting downstream effects that may be related to, or influenced by aberrations in gene expression, rather than targeting the up- or down-regulated transcripts themselves. This type of targeting can lead to significant off-target effects, which can translate to false positives for diagnostics, and systemic toxicity for therapeutics. This thesis discusses a nanoparticle-based conjugate which aims to increase the specificity of diagnostics, therapeutics, and biological research platforms by targeting RNA transcripts directly. This nanoconjugate, known as the spherical nucleic acid (SNA) is capable of entering live cells with negligible cytotoxicity and immunogenicity, and binding onto targeted RNA transcripts. Chapter one details the properties and synthesis of the SNA, and discusses how the cell entry/transcript binding capabilities of the SNA can be translated into therapeutic and diagnostic platforms. Chapter two then moves into the therapeutic applications of the SNA, discussing a novel platform known as the Sticky-flare, which is capable of detecting and fluorescently labeling target transcripts for real time analysis. Chapter three then investigates the function of the SNA in a therapeutic application. Specifically, the route that topically applied SNAs take to penetrate through skin is elucidated, and is contextualized by comparing the penetration of SNAs with equivalent linear DNA sequences. Linear nucleic acids are typically not capable of effecting gene regulation via topical application in the way that SNAs have been shown to, and the reasons for this are identified and examined. Finally, chapter five investigates whether super-porous materials such as metal organic frameworks (MOFs) are applicable as SNA cores, specifically I analyze if SNAs with a MOF core maintain the ability to enter cells in a way similar to gold core SNAs. It further investigates the complications of analyzing SNAs with high sedimentation rates (S) in cell culture, and the development of a novel method with which to analyze high-S nanoparticle structures. The conclusion of the thesis then mentions future applications of diagnostic and therapeutic SNAs, and how such nanostructures may play a role in molecular biology, as well as cancer diagnostics and therapeutics.

ISBN: 9781339786773Subjects--Topical Terms:

526235
Nanotechnology.

Investigation and Manipulation of the Local Microenvironment of Spherical Nucleic Acid Nanoconjugates.
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