Review Article
Polymer-Based Delivery of Glucagon-Like Peptide-1 for the Treatment of Diabetes
Table 2
Classification of expression vector system of GLP-1 or related mimetic gene in viral vectors.
| Delivery carriers | Therapeutic material | Expression vector system | Characterizations | Applications | In vivo injection route | Glycemic effect period | Diabetes type | Ref |
| Ad | GLP-1 | Ad-CUbiEX4GLP-1Gly8 | GLP-1 linked to Ex4 leader sequence with CMV enhancer/ubiquitin promoter and ubiquitin B intron (CUbi) in Ad gene | In vitro and in vivo (db/db mice or ZDF rats) | i.v. (1x) | 6 weeks | T2D | [36] |
GLP-1 | Ad2-CMV-GLP-1 |
GLP-1 driven by CMV promoter/-globin/IgG chimeric intron/albumin leder sequence in Ad2 gene | In vitro and in vivo (NOD/SCID or NOD mice) | i.v. (1x) | 30 dyas or 12 months | T1D | [37] | In vivo (ob/ob mice) | i.v. (1x) | 8 weeks | T2D | [37] | Exendin-4 | Helper-dependent Ad-CMV-exendin-4 | Exendin-4 expressed by CMV promoter/mouse IgG κ light chain leader/furin cleavage site in helper-dependent Ad gene | In vitro and in vivo (DIO mice) | i.v. (1x) | 15 weeks | T2D | [38] |
| Ad or AAV | GLP-1 | AAV- or Ad-IL-GLP-1 | GLP-1 driven by CMV promoter/-globin intron/insulin leader sequence in AAV or Ad gene | In vitro and in vivo (db/db mice or ZDF rats) | i.v. (1x) | 3 weeks | T2D | [39] |
| AAV | GLP-1 | dsAAV-MIP-GLP-1 | dsAAV8 vector containing GLP-1 gene expressed by mouse insulin-II promoter/proglucagon signal sequence | In vitro and in vivo (Balb/c) | i.p. (1x) | 3 weeks | T1D | [40] | GLP-1 | dsAAV-CB-GLP-1 | dsAAV2 containing GLP-1 expressed by CB promoter/Ig k-chain leader sequence/HA epitope tag/a furin protease recognition sequence | In vitro and in vivo (db/db mice) | i.v. (1x) | 4 months | T2D | [41] |
|
|
Ad: adenovirus. AAV: adeno-associated virus. dsAAV: double strand adeno-associated virus. CMV promoter: cytomegalovirus promoter. i.v., or i.p.: intravenous, or intraperitoneal injection. CB promoter: CMV enhancer/chicken -actin promoter. T1D or T2D: type 1 diabetes or type 2 diabetes.
|