Table 2.

Routes of administration for muscle-directed rAAV gene transfer.

	Advantages	Disadvantages	Route	Serotypes	Preclinical and clinical applications
Localized	Easy to administer High transduction in muscle	Not able to transduce large muscle mass	i.m.	AAV1	A1ATD [161], DMD [36,154] Hemophilia B [96], LGMD2D [162],
	Low off-target vector delivery				LPLD [163], XLMTM [197], Pompe disease [19]
	Low immune response			AAV2	A1ATD [169], DMD [164], McArdle disease [198]
				AAV6	Hemophilia B [104]
				AAV7	DMD [173,178], Pompe disease [172]
				AAV8	Heart failure [176]
				AAV9	Hemophilia B [185]
					DMD [189]
					CMD [192]
			t.v.p	AAV8	DMD [190]
				AAV2.5	DMD [34]
			i.c.i	AAV1	Heart failure [39]
				AAV2	Heart failure and LGMD [166]
				AAV6	Heart failure [177]
					Myocardial infarction [182]
				AAV9	Heart failure [195]
			r.c.d.	AAV1	Heart failure [160]
				AAV6	Heart failure [183]
			t.e.c.	AAV6	DMD [179], heart failure [180]
Systemic	Widespread transduction of large muscle mass, potentially the muscles of whole body	Off-target vector delivery Immune responses Need of high doses of vector Limited to certain rAAV serotypes	i.v.	AAV6	DMD [199], FSHD [174]
				AAV8	Heart failure [187], mouse [41]
				AAV9	DMD [45], mouse [56], heart failure [193], myocardial infarction [200]
			i.p.	AAV8	DMD [186]
				AAV9	LGMD [47]

A1ATD: α-1 anti-trypsin deficiency; AAV: Adeno-associated virus; CMD: Congenital muscular dystrophies; DMD: Duchenne muscular dystrophy; FSHD: Facioscapulohumeral muscular dystrophy; i.c.L: Intracoronary infusion; LGMD2D: Limb-girdle muscular dystrophy type 2D; LGMD: Limb-girdle muscular dystrophy; LPLD: Lipoprotein lipase deficiency; rAAV: recombinant adeno-associated virus; r.c.d: Recirculating delivery; t.e.c: Transendocardial injection; t.v.p.: Transvenous limb perfusion; XLMTM: X-linked myotubular myopathy.