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-1Gly^8	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/𝛽-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/𝛽-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 𝛽-actin promoter.
T1D or T2D: type 1 diabetes or type 2 diabetes.