Enlighten Theses
Source: https://theses.gla.ac.uk/9143/ Parent: https://theses.gla.ac.uk/view/subjects/QH345.html
Site navigation
Site tools
A-Z Lists
Enlighten Theses
- About
- Latest Additions
- Search
- Browse
- Browse by Year
- Browse by Subject
- Browse by College/School
- Browse by Author
- Browse by Funder
- ORCID
- My Thesis
- Login (Library staff only)
In this section
Engineering chimaeric recombinases for HIV-1 proviral DNA excision
Abioye, Jumai Adeola (2018) Engineering chimaeric recombinases for HIV-1 proviral DNA excision. PhD thesis, University of Glasgow.
Full text available as:
| PDF Download (12MB) |
Printed Thesis Information: https://eleanor.lib.gla.ac.uk/record=b3310662
Abstract
‘Cutting out’ HIV-1 proviral DNA could potentially cure a person of the infection. Genome editing approaches have been proffered for eradicating the provirus in infected persons by activating all latent viral reservoirs for further antiretroviral therapy or for the excision of the proviral DNA from memory T- cells. Previous approaches to do this have used nuclease-based tools or reprogrammed tyrosine recombinases; the former presenting unpredictable therapeutic outcomes and the latter, lengthy design time for newer tool variants if viral mutability erodes their effectiveness. Unlike nuclease-based tools that only cut DNA and rely on host-mediated repair mechanisms, chimaeric recombinases (CRs) cut DNA and carry the inherent ability to re-ligate cut ends at the cleavage site. The modular domain architecture of small serine recombinases can be redesigned to mediate site-specific recombination on non-cognate sites, by replacing the C-terminal DNA binding domains (DBDs) of serine recombinases with programmable DBDs such as Zinc Finger (ZF) proteins, TAL effector proteins and CRISPR-dCas9. For HIV-1 proviral DNA excision, CR requirement for the interaction of two recombinase-bound sites, and the lack of necessity for host cell-encoded factors should maximize the fidelity and efficiency of provirus removal.
In this work, the engineering and characterization of CRs with the specificity to recognize and promote site-specific recombination at highly conserved regions within the HIV-1 proviral DNA is explored. This research provides a solid proof-of-concept for the use of CRs to target divergent novel target sequences, expanding their applicability for applied genome editing and wider biotechnological applications.
| Item Type: | Thesis (PhD) |
| Qualification Level: | Doctoral |
| Keywords: | Chimaeric recombinase, genome editing, recombination, synthetic biology, protein engineering, bioengineering, molecular biology. |
| Subjects: | Q Science > QH Natural history > QH345 Biochemistry Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology |
| Colleges/Schools: | College of Science and Engineering > School of Engineering > Biomedical Engineering |
| Funder's Name: | Engineering and Physical Sciences Research Council (EPSRC) |
| Supervisor's Name: | Cooper, Professor Jonathan M., Reboud, Dr. Julien and Stark, Professor Marshall W. |
| Date of Award: | 2018 |
| Depositing User: | J.A. Abioye |
| Unique ID: | glathesis:2018-9143 |
| Copyright: | Copyright of this thesis is held by the author. |
| Date Deposited: | 29 May 2018 08:53 |
| Last Modified: | 17 Feb 2023 08:48 |
| Thesis DOI: | 10.5525/gla.thesis.9143 |
| URI: | https://theses.gla.ac.uk/id/eprint/9143 |
Actions (login required)
| View Item |
Downloads
Downloads per month over past year
Tools
RDF+XML RDF+N-Triples JSON RefWorks Dublin Core Atom Simple Metadata Refer METS HTML Citation ASCII Citation OpenURL ContextObject EndNote OpenURL ContextObject in Span MODS MPEG-21 DIDL EP3 XML Data Cite XML Reference Manager RDF+N3 Multiline CSV
\
Library
The University of Glasgow is a registered Scottish charity: Registration Number SC004401