{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/91595"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/91595","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Cationic, α-helical polypeptides for cell penetration and non-viral gene delivery","abstract":"Gene therapy is showing great potentials in treating various kinds of genetic diseases. The development of effective and safe delivery vectors are quite crucial towards gene therapy. Compared with viral vectors, non-viral gene delivery vectors allow the safe delivery of genetic materials with less inherent adverse reactions such as immunogenicity, unexpected viral replication and recombination, and oncogenicity. However, the non-viral vectors usually suffer from the low transfection efficiency due to various challenges and obstacles involved in the non-viral gene delivery process. The goal of my Ph. D. research is to develop the polypeptide-based non-viral gene delivery vectors to achieve excellent cell membrane penetration and gene delivery. Firstly, I modified the complexes from the development of the supramolecular structures via incorporating a sugar containing polypeptide to form the ternary complexes. The ternary complexes contain the membrane target polypeptide, which could facilitate the active targeting to the cells via the mannose-receptor mediated targeting, and the membrane active polypeptide, which could penetrate the cell membrane and allow the efficient gene delivery. Then, I use the chemical modification method to modify the polypeptides with the hydrophobic domain. A library of copolypeptides with different side chains modified by aromatic groups and aliphatic groups are synthesized and screened for cell penetration and gene delivery. This chemical modification strategy significantly enhances the penetration ability of the copolypeptides and allows the efficient penetration via multi-mechanisms: endocytosis, pore formation and the direct membrane translocation without generating pores. The screened copolypeptides could successfully deliver genes into cells demonstrated by both in vitro and in vivo experiments. Even though numbers of polypeptides have been successfully demonstrated as the excellent DNA delivery candidates, there still exist various barriers and obstacles in delivering siRNA. One of the limitations is the individual siRNA condensation by the helical polypeptides. To overcome the dearth of polypeptide mediated siRNA delivery, I develop the reversely crosslinked thiolated polypeptide to facilitate the siRNA condensation and significantly improve the stability of siRNA. This strategy allows the tight condensing and protection of the siRNA in the extracellular environment and the release of the siRNA in the intracellular environment. My Ph.D. research aims on the design of the cationic polypeptides as the novel non-viral gene delivery vectors and helps establish the design criteria of the cationic polymers by overcoming various gene delivery barriers.","abstract_html":"Gene therapy is showing great potentials in treating various kinds of genetic diseases. The development of effective and safe delivery vectors are quite crucial towards gene therapy. Compared with viral vectors, non-viral gene delivery vectors allow the safe delivery of genetic materials with less inherent adverse reactions such as immunogenicity, unexpected viral replication and recombination, and oncogenicity. However, the non-viral vectors usually suffer from the low transfection efficiency due to various challenges and obstacles involved in the non-viral gene delivery process. The goal of my Ph. D. research is to develop the polypeptide-based non-viral gene delivery vectors to achieve excellent cell membrane penetration and gene delivery. Firstly, I modified the complexes from the development of the supramolecular structures via incorporating a sugar containing polypeptide to form the ternary complexes. The ternary complexes contain the membrane target polypeptide, which could facilitate the active targeting to the cells via the mannose-receptor mediated targeting, and the membrane active polypeptide, which could penetrate the cell membrane and allow the efficient gene delivery. Then, I use the chemical modification method to modify the polypeptides with the hydrophobic domain. A library of copolypeptides with different side chains modified by aromatic groups and aliphatic groups are synthesized and screened for cell penetration and gene delivery. This chemical modification strategy significantly enhances the penetration ability of the copolypeptides and allows the efficient penetration via multi-mechanisms: endocytosis, pore formation and the direct membrane translocation without generating pores. The screened copolypeptides could successfully deliver genes into cells demonstrated by both in vitro and in vivo experiments. Even though numbers of polypeptides have been successfully demonstrated as the excellent DNA delivery candidates, there still exist various barriers and obstacles in delivering siRNA. One of the limitations is the individual siRNA condensation by the helical polypeptides. To overcome the dearth of polypeptide mediated siRNA delivery, I develop the reversely crosslinked thiolated polypeptide to facilitate the siRNA condensation and significantly improve the stability of siRNA. This strategy allows the tight condensing and protection of the siRNA in the extracellular environment and the release of the siRNA in the intracellular environment. My Ph.D. research aims on the design of the cationic polypeptides as the novel non-viral gene delivery vectors and helps establish the design criteria of the cationic polymers by overcoming various gene delivery barriers.","abstract_has_math":false,"creators":["Zheng, Nan"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Materials Science & Engr","degree_department":null,"school":null,"contributors":["Kilian, Kristopher","Cheng, Jianjun","Fan, Timothy M.","Lezmi, Stephane","Leal, Cecilia"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-09-09T21:14:41Z","date_published":"2016-09-09T21:14:41Z","updated_at":"2026-07-22T22:26:34Z","subjects":["Gene delivery","Non-viral","Polypeptide","Membrane penetration"],"languages":["en"],"rights":["Copyright 2015 Nan Zheng"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/91595","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kilian, Kristopher","Cheng, Jianjun","Fan, Timothy M.","Lezmi, Stephane","Leal, Cecilia"]},{"key":"dc:creator","label":"Author","values":["Zheng, Nan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2016-09-09T21:14:41Z","2018-09-09T09:15:11Z","2015-07-15","2015-08"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Materials Science & Engr"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Gene delivery","Non-viral","Polypeptide","Membrane penetration"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2015 Nan Zheng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/91595"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Gene therapy is showing great potentials in treating various kinds of genetic diseases. The development of effective and safe delivery vectors are quite crucial towards gene therapy. Compared with viral vectors, non-viral gene delivery vectors allow the safe delivery of genetic materials with less inherent adverse reactions such as immunogenicity, unexpected viral replication and recombination, and oncogenicity. However, the non-viral vectors usually suffer from the low transfection efficiency due to various challenges and obstacles involved in the non-viral gene delivery process. The goal of my Ph. D. research is to develop the polypeptide-based non-viral gene delivery vectors to achieve excellent cell membrane penetration and gene delivery. Firstly, I modified the complexes from the development of the supramolecular structures via incorporating a sugar containing polypeptide to form the ternary complexes. The ternary complexes contain the membrane target polypeptide, which could facilitate the active targeting to the cells via the mannose-receptor mediated targeting, and the membrane active polypeptide, which could penetrate the cell membrane and allow the efficient gene delivery. Then, I use the chemical modification method to modify the polypeptides with the hydrophobic domain. A library of copolypeptides with different side chains modified by aromatic groups and aliphatic groups are synthesized and screened for cell penetration and gene delivery. This chemical modification strategy significantly enhances the penetration ability of the copolypeptides and allows the efficient penetration via multi-mechanisms: endocytosis, pore formation and the direct membrane translocation without generating pores. The screened copolypeptides could successfully deliver genes into cells demonstrated by both in vitro and in vivo experiments. Even though numbers of polypeptides have been successfully demonstrated as the excellent DNA delivery candidates, there still exist various barriers and obstacles in delivering siRNA. One of the limitations is the individual siRNA condensation by the helical polypeptides. To overcome the dearth of polypeptide mediated siRNA delivery, I develop the reversely crosslinked thiolated polypeptide to facilitate the siRNA condensation and significantly improve the stability of siRNA. This strategy allows the tight condensing and protection of the siRNA in the extracellular environment and the release of the siRNA in the intracellular environment. My Ph.D. research aims on the design of the cationic polypeptides as the novel non-viral gene delivery vectors and helps establish the design criteria of the cationic polymers by overcoming various gene delivery barriers.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2017-08-01","The student, Nan Zheng, accepted the attached license on 2015-07-15 at 10:02.","The student, Nan Zheng, submitted this Dissertation for approval on 2015-07-15 at 10:14.","This Dissertation was approved for publication on 2015-07-15 at 15:20.","DSpace SAF Submission Ingestion Package generated from Vireo submission #8475 on 2016-09-09 at 16:06:54","Made available in DSpace on 2016-09-09T21:14:41Z (GMT). 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The development of effective and safe delivery vectors are quite crucial towards gene therapy. Compared with viral vectors, non-viral gene delivery vectors allow the safe delivery of genetic materials with less inherent adverse reactions such as immunogenicity, unexpected viral replication and recombination, and oncogenicity. However, the non-viral vectors usually suffer from the low transfection efficiency due to various challenges and obstacles involved in the non-viral gene delivery process. The goal of my Ph. D. research is to develop the polypeptide-based non-viral gene delivery vectors to achieve excellent cell membrane penetration and gene delivery. Firstly, I modified the complexes from the development of the supramolecular structures via incorporating a sugar containing polypeptide to form the ternary complexes. The ternary complexes contain the membrane target polypeptide, which could facilitate the active targeting to the cells via the mannose-receptor mediated targeting, and the membrane active polypeptide, which could penetrate the cell membrane and allow the efficient gene delivery. Then, I use the chemical modification method to modify the polypeptides with the hydrophobic domain. A library of copolypeptides with different side chains modified by aromatic groups and aliphatic groups are synthesized and screened for cell penetration and gene delivery. This chemical modification strategy significantly enhances the penetration ability of the copolypeptides and allows the efficient penetration via multi-mechanisms: endocytosis, pore formation and the direct membrane translocation without generating pores. The screened copolypeptides could successfully deliver genes into cells demonstrated by both in vitro and in vivo experiments. Even though numbers of polypeptides have been successfully demonstrated as the excellent DNA delivery candidates, there still exist various barriers and obstacles in delivering siRNA. One of the limitations is the individual siRNA condensation by the helical polypeptides. To overcome the dearth of polypeptide mediated siRNA delivery, I develop the reversely crosslinked thiolated polypeptide to facilitate the siRNA condensation and significantly improve the stability of siRNA. This strategy allows the tight condensing and protection of the siRNA in the extracellular environment and the release of the siRNA in the intracellular environment. My Ph.D. research aims on the design of the cationic polypeptides as the novel non-viral gene delivery vectors and helps establish the design criteria of the cationic polymers by overcoming various gene delivery barriers.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2017-08-01","The student, Nan Zheng, accepted the attached license on 2015-07-15 at 10:02.","The student, Nan Zheng, submitted this Dissertation for approval on 2015-07-15 at 10:14.","This Dissertation was approved for publication on 2015-07-15 at 15:20.","DSpace SAF Submission Ingestion Package generated from Vireo submission #8475 on 2016-09-09 at 16:06:54","Made available in DSpace on 2016-09-09T21:14:41Z (GMT). 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