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You searched for id:"oai:repository.cmu.edu:dissertations-1925". One record found.

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Carnegie Mellon University

1. Knapp, Christopher M. Engineering siRNA Lipid Nanoparticles for the Treatment of Mantle Cell Lymphoma.

Degree: 2017, Carnegie Mellon University

Mantle cell lymphoma (MCL) is an extremely difficult to treat subtype of non-Hodgkin lymphoma (NHL) with a low patient survival rate compared to most common cancers. Recently, nanoparticle delivery systems have received a great deal of interest for treating NHL. One of the more promising cargo options for these systems is short interfering RNA (siRNA). siRNA is a 18-23 nucleotide long double stranded RNA that is used to inhibit the protein expression of target mRNAs in a sequence specific manner. MCLs have several commonly overexpressed genes compared to normal cells making it an ideal candidate for siRNA therapies. For RNA interference to occur, A delivery vehicle is needed for the siRNA to reach the cytoplasm of the cell. In this thesis, ionizable lipid-like materials termed lipidoids are formulated into lipid nanoparticles (LNPs) to deliver siRNA. A new library of lipidoids is constructed to gain a better understanding of how the lipidoid tail-structure affects the silencing ability of LNPs. A novel tail precursor is identified as conferring potency to LNPs. Then, LNPs are used to silence genes within difficult to transfect MCL cells. LNPs targeting the anti-apoptotic protein Mcl-1 exhibit potent gene silencing and cause an increase in the fraction of cells undergoing apoptosis. This is important because there is no therapeutic that is FDA approved that targets this commonly overexpressed protein. Because of this LNP’s potency, siRNAs targeting multiple genes can be encapsulated into LNPs without causing unwanted toxicity. LNPs targeting several genes in multiple pathways cause a larger fraction of MCL cells to undergo apoptosis compared to cells treated with LNPs targeting only one gene. A major issue in cancer therapeutics is that the majority of nanoparticles accumulate in the liver. In an effort to improve the delivery of LNPs to target cells, changes to their formulations and administration methods are investigated as a means to improve LNP circulation time, biodistribution, and silencing ability. Overall, this work identifies lipidoid nanoparticles as potent siRNA delivery systems to treat MCL and investigates key properties for further improvement in LNP siRNA delivery to target cells.

Subjects/Keywords: drug delivery; lipidoid; nanoparticle; nanotechnology; non-Hodgkin lymphoma; siRNA

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Knapp, C. M. (2017). Engineering siRNA Lipid Nanoparticles for the Treatment of Mantle Cell Lymphoma. (Thesis). Carnegie Mellon University. Retrieved from http://repository.cmu.edu/dissertations/886

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Knapp, Christopher M. “Engineering siRNA Lipid Nanoparticles for the Treatment of Mantle Cell Lymphoma.” 2017. Thesis, Carnegie Mellon University. Accessed May 28, 2017. http://repository.cmu.edu/dissertations/886.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Knapp, Christopher M. “Engineering siRNA Lipid Nanoparticles for the Treatment of Mantle Cell Lymphoma.” 2017. Web. 28 May 2017.

Vancouver:

Knapp CM. Engineering siRNA Lipid Nanoparticles for the Treatment of Mantle Cell Lymphoma. [Internet] [Thesis]. Carnegie Mellon University; 2017. [cited 2017 May 28]. Available from: http://repository.cmu.edu/dissertations/886.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Knapp CM. Engineering siRNA Lipid Nanoparticles for the Treatment of Mantle Cell Lymphoma. [Thesis]. Carnegie Mellon University; 2017. Available from: http://repository.cmu.edu/dissertations/886

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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