Table 1.
Proteinaceous AAV receptors and their validation
| Proteinaceous receptor |
AAV Serotype |
Validation | Ref. | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Loss of function studies |
Overexpression studies in poorly permissive cell lines |
Ligand/ecto- domain inhibition assay |
Receptor antibody inhibition assay |
Binding assay | Internalization assay |
Biodistribution /infection correlation |
In vivo evaluation |
|||
| aVβ5 integrin | AAV2 | – | YES (CS-1 cells) | – | – | YES (virus overlay assay) | YES (immunofluorescence) | – | – | [66] |
| Fibroblast growth factor receptor-1 (FGFR1) | AAV2 | – | YES in conjunction with HSPG (Raji cells) | YES; ligand (NIH3T3 and 293 cells) | – | YES (enhanced binding to FGFR1/HSPG-overexpressing Raji cells) | – | – | – | [23] |
| AAV3H | – | – | YES; ectodomain (KB cells) | – | YES (dot blot) | – | – | – | [67] | |
| Hepatocyte growth factor receptor (c-MET) | AAV2 | – | YES (NIH3T3 cells) | YES; ligand (HeLa cells) | YES (NIH3T3 cells overexpressing c-MET) | YES (virus overlay assay) | YES (immunofluorescence) | – | – | [21, 68] |
| AAV3 | YES; siRNA (HuH7 cells) | – | YES; ligand (HuH7 cells) | YES (HeLa and HuH7 cells) | – | – | – | Poor murine transduction by AAV3 | [68] | |
| A5β1 integrin | AAV2 | – | YES (CHOB2 and CS1 cells) | YES; ectodomain (HEK293 cells) | YES (293 cells) | YES (Solid phase binding profiles) | YES (wt AAV2 vs R513A mutant) | – | YES (Comparison of wt AAV2 with R513A mutant) | [69] |
| CD9 tetraspanin | AAV2 | Yes; siRNA (MCF7 and T47D cells) | YES (T47D, BT8Ca, rat BT12Ca cells) | – | YES - only in low HSPG cells | – | – | YES (HSPG-low vs HSPG-high cell types) | – | [22] |
| Laminin receptor (LamR) | AAV8, AAV2, AAV3, AAV9 | Yes; siRNA (NIH3T3 cells) | YES (NIH3T3 cells) | YES; ligand for AAV8 (HeLa cells) | YES for AAV8 (HeLa cells) | YES - AAV2, AAV8 (yeast bait/prey assay) | – | – | YES for AAV2, AAV8 (antibody inhibition assay) | [26] |
| Platelet-derived growth factor receptor (PDGFR) | AAV5 | YES; siRNA (NIH3T3 cells) and inhibitor treatment (NCI60 cells) | YES (HeLa and 32D cells) | YES; both (32D (ligand) and Cos (ectodomain) cells) | YES (co-precipitation) | YES | YES (co-immunofluorescence studies in brain) | [24] | ||
| Epidermal growth factor receptor (EGFR) | AAV6 | YES; siRNA (HEK293, HN13 cells) | YES (32D cells) | – | – | YES (co-precipitation) | YES (inhibitor use) | YES | YES (tumor-specific reduction) | [25] |
| Adeno-associated virus receptor (AAVR) | AAV1, AAV2, AAV3B, AAV5, AAV6, AAV8, AAV9 | YES; CRISPR/Cas9 (HAP1, HeLa, HEK293, U2OS, HuH7, K562, MEF, A549 cells) | YES (Caco-2, NIH3T3, Raji, HT29 cells) | YES; ectodomain (HeLa cells) | YES (HeLa cells) | YES (ELISA, SPR) | – | – | YES (knock-out studies) | [27] |