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postgraduate thesis: Effective DNA delivery mediated by pH responsive peptides
Title | Effective DNA delivery mediated by pH responsive peptides |
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Authors | |
Issue Date | 2012 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Chan, F. [陳賦麟]. (2012). Effective DNA delivery mediated by pH responsive peptides. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4833333 |
Abstract | Non-viral vectors have been used to deliver therapeutic genes to treat different diseases. There are a variety of non-viral vectors such as liposomes, cationic polymers and peptides. Among all, pH responsive peptides showed excellent DNA transfection efficiency in many types of cell. These peptides are capable of changing their structural conformation as pH decreases, adopting a disordered structure which can destabilize endosomal membrane and therefore enhancing the release of DNA from endosomes into cytosol.
Traditional pH responsive histidine-rich peptides showed good DNA transfection efficiency and low toxicity to the cells when compared with other non-viral vectors. However, their low pKa value restricted these peptides to be protonated only at late endosomal stage, in which DNA is extremely susceptible to endosomal degradation. This hindered the DNA to be released to the cytosol efficiently and therefore reduced DNA transfection efficiency. In response to this, it is of great interest to probe into the insertion of either 2,3-diaminopropionic acid (Dap) or methylated-2,3-diaminopropionic acid Dap(Me) to the peptide as alternative pH sensitive components. The pKa values for both Dap and Dap(Me) peptides are higher than that of histidine. It is anticipated that the higher pKa value, the protonation of peptide could be happened at an earlier stage of endosomal maturation. Such protonation of peptide destabilizes the endosome membrane rapidly, causing the release of DNA to the cytosol effectively and hence improving DNA transfection efficiency.
In this experiment, LADap(Me)4-L1 peptide was the optimal candidate within the series. It showed good DNA transfection efficiency and cell viability in A549 cells among all Dap and Dap(Me) peptides. |
Degree | Master of Medical Sciences |
Subject | Peptides. Gene targeting. Genetic vectors. Gene therapy. |
Dept/Program | Pharmacology and Pharmacy |
Persistent Identifier | http://hdl.handle.net/10722/173921 |
HKU Library Item ID | b4833333 |
DC Field | Value | Language |
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dc.contributor.author | Chan, Fu-lun. | - |
dc.contributor.author | 陳賦麟. | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | Chan, F. [陳賦麟]. (2012). Effective DNA delivery mediated by pH responsive peptides. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4833333 | - |
dc.identifier.uri | http://hdl.handle.net/10722/173921 | - |
dc.description.abstract | Non-viral vectors have been used to deliver therapeutic genes to treat different diseases. There are a variety of non-viral vectors such as liposomes, cationic polymers and peptides. Among all, pH responsive peptides showed excellent DNA transfection efficiency in many types of cell. These peptides are capable of changing their structural conformation as pH decreases, adopting a disordered structure which can destabilize endosomal membrane and therefore enhancing the release of DNA from endosomes into cytosol. Traditional pH responsive histidine-rich peptides showed good DNA transfection efficiency and low toxicity to the cells when compared with other non-viral vectors. However, their low pKa value restricted these peptides to be protonated only at late endosomal stage, in which DNA is extremely susceptible to endosomal degradation. This hindered the DNA to be released to the cytosol efficiently and therefore reduced DNA transfection efficiency. In response to this, it is of great interest to probe into the insertion of either 2,3-diaminopropionic acid (Dap) or methylated-2,3-diaminopropionic acid Dap(Me) to the peptide as alternative pH sensitive components. The pKa values for both Dap and Dap(Me) peptides are higher than that of histidine. It is anticipated that the higher pKa value, the protonation of peptide could be happened at an earlier stage of endosomal maturation. Such protonation of peptide destabilizes the endosome membrane rapidly, causing the release of DNA to the cytosol effectively and hence improving DNA transfection efficiency. In this experiment, LADap(Me)4-L1 peptide was the optimal candidate within the series. It showed good DNA transfection efficiency and cell viability in A549 cells among all Dap and Dap(Me) peptides. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.source.uri | http://hub.hku.hk/bib/B48333335 | - |
dc.subject.lcsh | Peptides. | - |
dc.subject.lcsh | Gene targeting. | - |
dc.subject.lcsh | Genetic vectors. | - |
dc.subject.lcsh | Gene therapy. | - |
dc.title | Effective DNA delivery mediated by pH responsive peptides | - |
dc.type | PG_Thesis | - |
dc.identifier.hkul | b4833333 | - |
dc.description.thesisname | Master of Medical Sciences | - |
dc.description.thesislevel | Master | - |
dc.description.thesisdiscipline | Pharmacology and Pharmacy | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.5353/th_b4833333 | - |
dc.date.hkucongregation | 2012 | - |
dc.identifier.mmsid | 991033832929703414 | - |