Table 3.

Overview of some AAV pre-clinical studies using systemic gene delivery to treat various animal models of LSDs (vg: vector genomes; gc: genome content, equivalent of vg; iu: infective units; P: Post-natal day).

Delivery Route	Disease	Species	Model	Vector	Dose	Time of injection	Ref.
Tail Vein
	Gaucher	Mouse	UBC-creERT2-Gbaflox/flox	AAV9-CMV-Gba or AAV9-SYN-Gba	3–5 × 1011 vg	4 weeks	[134]
	GM1	Mouse	C57BL/6J-βgal−/−	AAV9-CAG-βgal	1 × 1011 or 3 × 1011 vg	6 weeks	[135]
	GM2 (Sandhoff)	Mouse	C57BL/6:C129-Hexb−/−	AAV9-CMV-HEXB	2.5 × 1014 or 3.5 × 1013 vg/kg	P1 or 6 weeks	[136]
	GM2 (Sandhoff)	Mouse	Hexb−/−	AAV9 or PHP.B-BiCBA-mHEXA/mHEXB, AAV9 or PHP.B-P2-HEX	AAV9: 1 × 1012–4 × 1012 vg; PHP.B: 3 × 1011–1 × 1012 vg	4 weeks	[137]
	Krabbe	Mouse	C57BL-twi/twi	AAVhr10-CAG-mGALC	2 × 1011 vg	P10–12	[138]
	MPS I	Mouse	C57BL/6-Idua−/−	AAV9-CAG-IDUA or AAVrh10-CAG-IDUA	1 × 1012 vg	8–21 weeks	[139]
	MPS II	Mouse	idsy/-	AAV8-EF1α-IDS	1 × 1011 vg	NA	[140]
	MPS IIIA	Mouse	C57BL/6-Sgsh−/−	scAAVrh74-U1a-hSGSH	5 × 1012 vg/kg	4–6 weeks	[141]
	MPS IIIA	Mouse	C57BL/6-SgshG91A	AAV9-CAG-mSGSH	1 × 1012 vg	2 months	[142]
	MPS IIIB	Mouse	C57BL/6-Naglu−/−	AAV9-CAG-hNAGLU	1 × 1013 vg/kg	4–6 weeks	[143]
	MPS IIIB	Mouse	C57BL/6-Naglu−/−	AAV2-CMV-hNAGLU	4 × 1011 vg	4–6 weeks	[144]
	MPS VII	Mouse	b6.C-H-abm1/byBir-gusmps/mps	AAV9-βGluc	1 × 1012 vg	6 weeks	[145]
Temporal/Cephalic Vein
	Gaucher	Mouse	CD1-K14-ln/ln	AAV9-GUSB-hGBA1	4 × 1011 gc	P0–P1	[146]
	Gaucher	Mouse	CD1-K14-ln/ln	AAV9-SYN-hGBA1	2.4 × 1012 vg	P0–P1	[147]
	MPS I	Mouse	Idua −/−	AAV2-CAG-hIDUA	1010 vp	P1–P2	[148]
	MPS II	Mouse	idsy/-	AAV5-CMV-hIDS	1 × 1011 vg	P2	[149]
	MPS VII	Mouse	B6.C-H-2bm1/ByBir-gusmps/mps	AAV-CAG-hGUSB	5 × 109 iu/kg	P2	[150]
	MPS VII	Mouse	B6.C-H-2bm1/ByBir-gusmps/mps	AAV-CAG-hGUSB	8 × 1010 iu/kg	P2	[151]
	MSD	Mouse	C57B6/S129J-Sgsh−/−	AAV9-CMV-hSUMF1	2 × 1011 vg	P1	[152]
Jugular Vein
	MLD	Mouse	C57BL/6-ASA−/−	AAV9-CAG-hARSA	2 × 1012 vg	P1–2	[153]
Retro-orbital Sinus
	Pompe	Mouse	C57BL/6J-GAA−/−	AAV-PHP.B-CAG-hGAA	5 × 1012 vg/kg	2 weeks	[154]
Combination
IV + ICV	MSD	Mouse	C57B6/S129J-Sgsh−/−	AAV9-CMV-hSUMF1	IV: 2 × 1011 vg; ICV: 6 × 109 vg	P1	[152]
IV + IT	MPS VII	Mouse	C57BL6/J-Gusb/b	AAV2-CMV-GUSB	IV: 4.1 × 1011 vg; IT: 3 × 1010 vg	P3–P4	[155]
IV + CM	MPS IIIB	Mouse	C57BL/6-Naglu−/−	AAV2-CMV-hNAGLU	IV: 4 × 1011 vg; CM: 5 × 1010 vg	4–8 weeks	[156]