Abdo, Ahmad Ismail Khaled (2024) A Single Domain Antibody Derived From Antibody Phage Display Library Fused With Cell Penetrating Peptide For The Clearance Of Il-23. PhD thesis, Perpustakaan Hamzah Sendut.
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Abstract
Il-23 is a two-subunit proinflammatory cytokine that plays an important role in shaping the immune response. It is associated with several autoinflammatory diseases by generating sustained inflammatory loops through the il-17 and il-22 arms leading to tissue damage. Antibody neutralization of il-23 was proven to be effective in breaking these loops and ameliorating disease. However, antibodies have limited tissue penetration and tend to elicit anti-drug antibodies due to their large size. Additionally, anti-il-23 antibodies target only one subunit of the cytokine, either p40 or p19, leaving the other one unneutralized. This study aimed to generate an anti-il-23 single domain antibody (sdab) that leads to antigen-clearance. Two methods of antigen clearance were explored, the isolation of a recycling sdab by phage display and conjugation of sdab to cell penetrating peptides (cpps). The sdab was generated by phage display biopanning against one of the il-23 subunits, p19, which was expressed in e.Coli fused to gamillus (gam) protein as a stabilizer. Biopanning failed to isolate specific, high-affinity recycling binders for p19, however, a specific and high-affinity standard binder for p19 was successfully isolated. The isolated sdab, designated as h11, was conjugated with two cpps, r9 and tatk, respectively. Elisa results of p19 binding to purified h11, h11-r9, and h11-tatk , showed that cpps conjugation did not alter the h11 binding affinity. The functionality of the purified sdabs was further examined to evaluate the cpp fusion effect.
| Item Type: | Thesis (PhD) |
|---|---|
| Subjects: | R Medicine > R Medicine (General) > R5-920 Medicine (General) |
| Divisions: | Pusat Pengajian Siswazah Perniagaan (Graduate School of Business) > Thesis |
| Depositing User: | Mr Hasmizar Mansor |
| Date Deposited: | 11 Feb 2026 07:02 |
| Last Modified: | 11 Feb 2026 07:17 |
| URI: | http://eprints.usm.my/id/eprint/63566 |
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