Identification of optimal target sequences for antisense-, ribozyme-, and decoy-mediated gene inhibition

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Title Identification of optimal target sequences for antisense-, ribozyme-, and decoy-mediated gene inhibition
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Chen, Zhidong
Date 1999-05
Description Antisense oligonucleotides, ribozymes, and transcription factor decoys are nucleic acid based agents. They inhibit target gene expression in a sequence-specific manner, and therefore, have great therapeutic potential. Currently, a relatively effective antisense, ribozyme, or decoy sequence is identified by testing the inhibitory activity of a series of sequences individually. Because the number of potential sequences that need to be tested is much greater than the number of sequences that can be, or is actually, tested individually, it is unlikely that the most effective sequences are identified. Due to the lack of suitable means to identify optimal or effective sequences against specific genes, it is not uncommon that a chosen sequence fails to inhibit or poorly inhibits the expression of a target gene. In this dissertation, I describe the development of a library approach for the identification of optimal antisense, ribozyme, and decoy sequences against the expression of specific genes. For this approach, libraries of antisense RNAs, ribozymes, and decoys with distinctive nucleotide sequences are derived directly from a target gene. Screening these so-called directed libraries in target cells allows the identification of the antisense, ribozyme, and decoy sequences that can ablate the expression of the target gene. I demonstrate the effectiveness of this approach by identifying the optimal antisense, ribozyme, and decoy sequences against the expression of lacZ' gene in Escherichia coli. This approach should be generally applicable for the identification of optimal antisense, ribozyme, and decoy sequences against any gene of interest.
Type Text
Publisher University of Utah
Subject Nucleotide sequence; Gene expression
Subject MESH Oligonucleotides; Gene Therapy; Anticarcinogenic Agents; Gene Expression; Ribosomes; Escherichia coli
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Identification of optimal target sequences for antisense-, ribozyme-, and decoy-mediated gene inhibition". Spencer S. Eccles Health Sciences Library.
Rights Management © Zhidong Chen.
Format application/pdf
Format Medium application/pdf
Format Extent 2,451,829 bytes
Identifier undthes,4222
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Funding/Fellowship NIH Grant (5R29AI34278); University of Utah Graduate Research Fellowships
Master File Extent 2,451,931 bytes
ARK ark:/87278/s6kh0q5w
Setname ir_etd
ID 191686
Reference URL https://collections.lib.utah.edu/ark:/87278/s6kh0q5w
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