Table 2.
Summary of AAV delivery by FUS-BBBO in mice, rats, and NHPs.
| Animal | AAV parameters | FUS parameters | Ref | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Animal | Target | Serotype | Gene | Dose (vg/g) | Microbubble (MB) Dose | Frequency (MHZ) |
Pressure (MPa) |
PRF (Hz) |
Pulse length (ms) |
Duration (s) | |
| Mouse | CT, STR, HP, TH | AAV9 | GFP | 5×108 2.5×109 1.25×1010 |
40–80 μL/kg | 0.558 1.18 |
0.3 0.53–0.6 |
1 | 10 | 120 | [130] |
| HP, CT | AAV9 | mcherry-ChR2 | 4×1011 vg/animal | 5 μL | 1.5 | 0.74 | 5 | 10 | 120 | [145] | |
| HP, SN, OB, DMV | AAV9 | 1.25×1010 | 0.02 mL/kg | 1.68 | 1.0 ± 0.2 1.1 ± 0.2 |
1 | 10 | 120 | [146] | ||
| STR, HP, midbrain | AAV9 |
6.7×109
1.3×109 |
1.5×106 MB | 1.5 | 0.33 | 1 | 10 | 120 | [147] | ||
| Whole brain | AAV9 | GFP | 1.1×1011 vg/animal |
8 μL/mL at 100 μL volume | 1.5 | 0.57 | 10 | 99 | 150 | [148] | |
| HP | AAV9 | GFP | 6.5×1010
1.0×1010 1.3×1011 vg/animal |
3.6×108 MBs/mL | 1.5 | 1.0 | 0.33 | 1.0 3.33 6.67 |
120 | [149] | |
| STR, TH | AAV9 | GFP | 1×1011
1.3×1010 |
0.02 mL/kg | 1.78 | 0.06 0.12 0.25 0.38 |
0.5 | 10 | 120 | [150] | |
| Large brain regions | AAV9 | GFP | 1×1010 | 1.5×106 MBs | 1.53 | 0.27 | 1 | 10 | 30 | [151] | |
| HP | AAV9-hM4Di | mcherry | 1×1010 | 1.5×106 MBs | 1.5 | 0.42 | 1 | 10 | 120 | [152] | |
| CT | AAV9, PHP.B |
1×1011 vg/animal |
1.5×107 MBs in 50 μL volume | 1.5 | 0.51 | 5 | 1.0 | 660 | [153] | ||
| CT, STR, TH | AAV9, PHP.B |
GFP | 1×1010
1×1011 |
0.02 mL/kg | 1.68 to 1.78 | ~0.5 – 2.0 | 1 | 10 | 120 | [139] | |
| HP | AAV9 AAV1 |
mcherry-ChR2 | 2.48×1012 vg/animal |
~2.5×107 MBs | 1.5 | 0.45 | 5 | 6.7 | 60 | [154] | |
| STR, TH | AAV9 AAV2-HBKO |
GFP | 1.7×109 3.3×109 1.7×1010 |
0.02 mL/kg | 0.58 | NA | 1 | 10 | 120 | [155] | |
| STR, HP, TH, CT | AAV6 AAV1/2 AAV9 |
GFP | 3×109 | 0.02 mL/kg | 1.68 | NA | 1 | 10 | 120 | [156] | |
| CT, STR, TH, HP | AAV1, 2, 5, 8, 9, rg | TdTomatoGFP | 3.33×109
1.67×1010 |
0.02 mL/kg | 0.58 | <0.9 | 1 | 10 | 180 | [131] | |
| STR | AAV2 | hrGFP | 1×109 | 0.3 mL/kg | 1.5 | 0.44 0.53 0.7 |
1 | 10 | 120 | [136] | |
| CPu | AAV1 | GFP | 1.1×1011 vg/animal |
~2.5×107 MBs | 1.5 | 0.45 | 5 | 20 | 300 | [138] | |
| CT, HP | AAV1/2 | GFP | 3×109 | 0.02 mL/kg | 1.68 | NA | 1 | 10 | 120 | [157] | |
| HP | AAV9-Cu64 | PKM2 | 2×1011 5×1011 vg/animal |
2.5×108 MBs/kg | 1.5 | 0.42 0.6 0.74 |
NA | NA | 120 | [158] | |
| Rat | Left brain | AAV2/1 | LacZ | 1.06×1011 vg/animal | 0.2×109 MBs/mL | 0.5 | 1.1 | 1 | 10 | 40+ | [159] |
| STR | AAV1/2 | GFP | 1×109 | 0.4×108 − 0.64×108 MBs/kg | 0.97 | 1 | 10 | 200 | [137] | ||
| STR, SN | AAV2 | NA | 2.96×1012 − 3.94×1012 vg/animal |
NA | 0.58 | 0.4 | 1 | 10 | 120 | [160] | |
| NHP | CT, TH, ST midbrain | AAV9-PHP.eB AAV9.2-PHP.eB |
GFP | 5×1013 vg/animal |
4 μL/kg | 0.220 | 1 Watts | NA | NA | 60 to 150 | [143] |
| CT | AAV2 AAV9 |
EGFP mCherry |
NA | 200 μL/kg | 1.46 | 1.17 | 1 | 10 | 60 | [144] | |
CT: Cortex; STR: Striatum; HP: Hippocampus; TH: Thalamus; CPu: Caudate putamen; Cd: Caudate nucleus; SN: Substantia nigra; OB: Olfactory bulb; DMV: Dorsal motor nucleus of the vagus; STN: Subthalamic nucleus; NHP: Non-human primates.