Table 1.
Viral-based vectors used for transduction of cells of the alveolar epithelium in vivo and alveolar type 2 cells in vitro
| Vector | Serotype or Envelope | Transgene | AT2 Cell-Specific Ex Vivo or In Vivo Model System(s) | Vector Dose | References |
|---|---|---|---|---|---|
| AdV-based vector | Ad5 | β-Galactosidase (LacZ) | Human fetal lung AT2 cells and fibroblast cocultures | 1.0 × 103 p/cell | 86 |
| Human fetal lung explants (22 weeks gestation) | 1.0 × 1011 p/explant | ||||
| Mouse lungs | 2.5 × 1011 p/mouse, IT | ||||
| SP-C1–197, SP-CΔexon4 | Mouse AT2 cells | 50 MOI | 35 | ||
| GFP, Bcl-xL, Bcl-2 | Mouse lungs | 2.0 × 1010 optical particle unit/mouse, IT | 87 | ||
| Mouse AT2 cells | 2.0 × 107–2.0 × 109 PFU/well | ||||
| FoxM1B, FoxM1B-TA, LacZ | Mouse AT2 cells | 20 MOI | 88 | ||
| Mouse lungs | 5.0 × 108 PFU, IT | ||||
| ABCA3 variants | Isolated human precursor lung epithelial cells | 3.0 × 103 VP/cell | 72 | ||
| AAV-based vector | AAV1 | hALP | Mouse lungs | 6.0 × 1010–3.0 × 1011 GC/mouse, IN | 98 |
| AAV2 | LacZ | Mouse lungs | 1.0 × 1010 p/mouse, IN | 97 | |
| GFP | Human embryonic stem cell-derived lung bud organoids | 3.5 × 108–1.0 × 109 GC | 103 | ||
| AAV4 | GFP | Pig lungs | 1.0 × 1012 VG/pig (bronchoscope-guided delivery to left lobe) | 100 | |
| AAV5 | hALP | Mouse lungs | 6.0 × 1010–3.0 × 1011 GC/mouse, IN | 98 | |
| LacZ | Mouse lungs | 1.0 × 1010 p/mouse, IN | 97 | ||
| AAV6 | ffLuc, hALP | Mouse lungs | 1.0 × 1011 VG/mouse, IN | 99 | |
| GFP | Human embryonic stem cell-derived lung bud organoid | 3.5 × 108–1.0 × 109 GC | 103 | ||
| AAV6.2 | GFP | Human embryonic stem cell-derived lung bud organoid | 3.5 × 108–1.0 × 109 GC | 103 | |
| AAV6.2FF | ffLuc, hALP | Mouse lungs | 1.0 × 1011 VG/mouse, IN | 99 | |
| GFP | Human embryonic stem cell-derived lung bud organoid | 3.5 × 108–1.0 × 109 GC | 103 | ||
| mSftpb, hSFTPB, GFP, mCherry, ffLuc | Mouse lungs | 1.0 × 1011 VG/mouse, IT | 104 | ||
| Precision cut lung slices (human) | 1.0 × 108–1.0 × 1010 VG | ||||
| mCherry, Cre, Sftpc-miR | Mouse lungs | 5.0 × 1011–4.0 × 1012 VG/mouse, IN | 105 | ||
| AAV8 | ACE2, GFP | Mouse lungs | 4.0 × 1011 VP/mouse, IT | 101 | |
| AAV9 | LacZ, α1-antitrypsin | Mouse lungs | 1.0 × 1011 GC/mouse, IN | 102 | |
| LV-based vector | VSV-G | EGFP | Rat AT2 cells | 0.1–50 MOI | 108 |
| EGFP | Mouse lungs | 1.0 × 108 international units, IT | 110 | ||
| CDK4, hTERT, SV40 | Human AT2 cells | Not available | 109 | ||
| GFP | iPSC-derived AT2 cells | 50 MOI | 111 | ||
| GFP | Mouse lungs | 0.5–3.0 × 108 TU/mouse, IT | 116 | ||
| SARS-CoV2 Spike | GFP | iPSC-derived AT2 cells | 30 MOI | 111 | |
| Sendai Virus—F and HN proteins | ffLuc | Mouse lungs | 5.0 × 108 TU/mouse, IN | 117 | |
| Mokola virus glycoprotein | GFP | Mouse lungs | 0.5–3.0 × 108 TU/mouse, IT | 116 | |
| Lymphocytic choriomeningitis virus glycoprotein | GFP | Mouse lungs | 0.5–3.0 × 108 TU/mouse, IT | 116 | |
| Ebola virus glycoprotein | GFP | Mouse lungs | 0.5–3.0 × 108 TU/mouse, IT | 116 |
AAV, adeno-associated virus; ABCA3, ATP-binding cassette transporter A3; AdV, adenovirus; AT2, alveolar type 2; ffLuc, firefly luciferase; GC, genome copies; hALP, human placental alkaline phosphatase; IN, intranasal; iPSC, induced pluripotent stem cell; IT, intratracheal; LV, lentivirus; MOI, multiplicity of infection; p, particles; PFU, plaque-forming unit; SP-C, surfactant protein C; VG, vector genomes; VP, viral particles; VSV-G, vesicular stomatitis virus glycoprotein.