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Jakobsson, Eric Jakobsson, Eric Blanke, Steven Sinha, Saurabh Kuhlman, Thomas DeVille, Lee Kotil, Seyfullah Enes 2017-03-01T17:01:50Z 2017-03-01T17:01:50Z 2019-03-02T10:15:07Z 2016-12-02 2016-12 In chapter 1 we have investigated the different requirements and conditions for efficiency and specificity of antisense molecules. For specific therapy, an antibacterial RNA must be able to distinguish between its designed targets and its off-targets. This distinction is reflected in the binding energy calculations. The major component of efficiency and specificity is uncovered to be the nature of the off-targets. We have made a new thermodynamic based model to explain in-vivo antisense binding. We have shown that it fits previously unexplained experimental data perfectly. The second chapter deals with how to preserve effective therapy in evolving population. The effectiveness of redesigning on resistance is conditioned on rescuing the hybridization affinity. The hybridization affinity can be rescued if the mutations for acquiring resistance were on the target sequence. However there can be mutations elsewhere in the genome that would confer resistance. We have investigated possible therapy strategies to direct the bacteria to take mutations that are on the target. Having multiple entry mechanisms for RNA therapy seems to be the key to directing bacteria towards a sustainable therapy. Third chapter deals with the following: Using antisense therapy to block progression of antibiotic resistance for trimethoprim. Converge bacteria to desired mutations. Using antisense molecules to induce loss of trimethoprim resistance mutations Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2018-12-01 The student, Seyfullah Kotil, accepted the attached license on 2016-12-01 at 00:49. The student, Seyfullah Kotil, submitted this Dissertation for approval on 2016-12-01 at 01:01. This Dissertation was approved for publication on 2016-12-02 at 14:50. DSpace SAF Submission Ingestion Package generated from Vireo submission #10389 on 2017-02-28 at 14:42:40 Made available in DSpace on 2017-03-01T17:01:50Z (GMT). No. of bitstreams: 2 KOTIL-DISSERTATION-2016.pdf: 11114319 bytes, checksum: 0f499da39beb5807021a14bda0191c28 (MD5) LICENSE.txt: 4212 bytes, checksum: cab45d034a2086db8e9d742e4334e8f6 (MD5) Previous issue date: 2016-12-02 Embargo set by: Seth Robbins for item 98716 Lift date: 2019-03-01T17:02:22Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system Embargo set by: Seth Robbins for item 98716 Lift date: 2019-03-01T17:03:32Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system Embargo set by: Seth Robbins for item 98716 Lift date: 2019-03-01T17:05:02Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system Embargo set by: Seth Robbins for item 98716 Lift date: 2019-03-01T17:06:55Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system Limited Restriction Lifted for Item 98716 on 2019-03-02T10:15:07Z. application/pdf http://hdl.handle.net/2142/95600 en Copyright 2016, Seyfullah Enes Kotil Antibiotic resistance Evolution of antibiotic resistance designing antisense molecules off-target sustainable therapy reversing antibiotic resistance blocking antibiotic resistance guiding antibiotic resistance directed evolution Requirements and strategies for winning the battle against antibiotic resistance by antisense technology text text School of Molecular & Cell Bio Biophysics & Computnl Biology University of Illinois at Urbana-Champaign Dissertation Ph.D.