Table 7 Preclinical studies on systemic-administered, AAV-based gene editing therapies for treating Duchenne muscular dystrophy (DMD)

Double-cut editing

 Exon 23 excision

mdx

AAV9

i.p.; i.v

2 × 10¹⁴ vg/ml—30 µl for i.p.; 90 µl for i.v

2:1:1

TA, heart

[123]

 Exon 23 excision

mdx

AAV8

i.p.; i.v

5.6 × 10¹¹ vg for i.p.; 5.4 × 10¹² vg for i.v

1:1

Abdominal, diaphragm, heart, TA

[124]

[125]

 Exon 23 excision

mdx

AAV9

i.p.; i.v

3 × 10¹² vg for i.p.; 3.6 × 10¹² vg for i.v

1:1

Heart, gastroc, TA, diaphragm, abdominal, triceps, quads,

[128]

 Exon 23 excision

mdx

AAV9

i.v

1.08 × 10¹³ or 4 × 10¹⁴ vg

2:1 or 1:3

Heart, quads, gastroc

[122]

 Exon 21–23 excision

mdx/Utr^+/−

AAVrh.74

i.v

1 × 10¹² vg

Single vector

Heart

[129]

 Exon 21–23 excision

mdx

AAVrh.74

i.p

1 × 10¹² vg

Single vector

Heart

[126]

 Duplicated exon 18–30 excision (targeting exon 21)

Dup18-30

AAV9

i.v

3 × 10¹² vg

Single vector

Heart, TA, triceps, diaphragm

[127]

 Formation of hybrid exons 47 & 58

Δ52hDMD/mdx

AAV9

i.v

7.5 × 10¹³ vg/kg

1:1

Heart

[121]

 Exon 52–53 excision

mdx^4cv

AAV6

i.v

1.4 × 10¹³ vg

5:2

TA, diaphragm, soleus, gastroc

[130]

Single-cut editing

 Exon 45 skipping/reframing

ΔEx44

AAV9

i.p

3 × 10¹⁴ or 5.5 × 10¹⁴ vg/kg

1:5 or 1:10

Heart, TA, diaphragm

[133]

 Exon 45 skipping/reframing

ΔEx44

scAAV9

i.p

8.4 × 10¹³–1.6 × 10¹⁴ vg/kg

Ranging from 1:0.05 to 1:1

Heart, TA, triceps, diaphragm

[134]

 Exon 51 skipping/reframing

ΔEx50

AAV9

i.p

6.3 × 10¹⁰ vg

n/a

Heart, triceps, gastroc, plantaris, quads, diaphragm

[132]

 Exon 51 skipping/reframing

ΔEx50-Dmd-Luc

AAV9

i.p

3 × 10¹⁴ vg/kg

1:2

Heart, TA, triceps, diaphragm

[137]

 Exon 51 skipping/reframing

ΔEx50

AAV9

i.p

2 × 10¹⁴ or 4 × 10¹⁴ vg/kg

Single vector

Heart, TA, triceps, diaphragm

[136]

 Exon 51 skipping/reframing

ΔEx50;h51KI

AAV9

i.p

1.6 × 10¹⁴ vg/kg

1:1

Heart, TA, triceps, diaphragm

[135]

Exon knockin

 Insertion of exon 52 or superexon 52–79

Δ52hDMD/mdx

AAV9

i.v

8.64 × 10¹¹ or 7 × 10¹¹ vg

1:1 or 1:5

Heart

[142]

Base editing

 CBE, exon 4 skipping

Dmd^E4*

AAV9

i.p

1.1 × 10¹² vg

1:1

Heart, TA, diaphragm, quads

[148]

 ABE, exon 53 mutation correction

mdx^4cv

AAV9

i.v

1 × 10¹⁴ vg/kg

1:2 (in split constructs)

Heart, gastroc, diaphragm

[151]

 ABE, exon 45 skipping

ΔEx44

AAV9

i.v

1.5 × 10¹⁴ & 3 × 10¹⁴ vg/kg

1:1

Heart, TA

[149]

 ABE, exon 50 skipping

ΔEx5051;h50KI

AAV9

i.p.; i.v

1 × 10¹⁴ vg/kg

1:3 (in split constructs)

Heart, TA, diaphragm

[150]