TABLE 2.
Examples of current clinical trials for adeno‐associated virus (AAV)‐based in vivo gene therapies, grouped by indication
| Viral vector | Serotype | Gene of interest | Indication | Name (Sponsor) | Route | Trial number |
|---|---|---|---|---|---|---|
| Ophthalmological diseases (n = 40) | ||||||
| AAV | AAV4D‐R100 | RPGR | Retinitis pigmentosa (X‐Linked) | 4D‐125 (4D Molecular Therapeutics) | Intravitreal | NCT04517149 (Phase 1/2) |
| AAV | AAV2 | sCD59 | Age‐related macular degeneration (Dry) | AAVCAGsCD59 (Hemera Biosciences) | Intravitreal | NCT04358471 (Phase 2) |
| AAV | AAV2 | ND4 | Leber hereditary optic neuropathy | GS010, aka Lenadogene Nolparvovec (GenSight Biologics) | Intravitreal | NCT03406104 (Phase 3) |
| AAV | AAV2 | REP1 | Choroideremia | BIIB‐111 (NightstaRx Ltd) | Subretinal | NCT03507686 (Phase 2) |
| AAV | AAV2tYF | CNGA3 | Achromatopsia | AGTC‐402 (Applied Genetic Technologies Corp) | Subretinal | NCT02935517 (Phase 1/2) |
| AAV | AAV2 | hRPE65 | Leber congenital amaurosis | Voretigene Neparvovec (Novartis) | Subretinal | NCT04516369 (Phase 3) |
| AAV | AAV2/8 | hCYP4V2 | Bietti's crystalline dystrophy | rAAV2/8‐hCYP4V2 (Beijing Tongren Hospital) | Subretinal | NCT04722107 (Phase 1) |
| AAV | AAV8 | Anti‐VEGF fab | Diabetic retinopathy | RGX‐314 (Regenxbio Inc.) | Intrasuprachoroidal | NCT04567550 (Phase 2) |
| AAV | AAV2tYF | hRS1 | X‐linked retinoschisis | rAAV2tYF‐CB‐hRS1 (Applied Genetic Technologies Corp) | Subretinal | NCT02416622 (Phase 1/2) |
| Neurological diseases (n = 28) | ||||||
| AAV | AAV9 | hSMN | Spinal muscular atrophy | Onasemnogene Abeparvovec‐xioi (Novartis) | Intravenous | NCT03505099 (Phase 3) |
| AAV | AAV9 | GBA1 | Parkinson's disease | PR001A (Prevail Therapeutics) | Intracranial | NCT04127578 (Phase 1/2) |
| AAV | AAV2 | AADC | Aromatic L‐amino acid decarboxylase (AADC) deficiency | AAV2‐Haadc (University of California, San Francisco) | Intracerebral | NCT02852213 (Phase 1) |
| AAV | AAVrh.10 h | hAPOE2 | Alzheimer disease | AAVrh.10 hPOE2 (Weill Medical College of Cornell University) | Intracranial | NCT03634007 (Phase 1) |
| AAV | AAVrh.10 | hGALC | Krabbe disease | FBX‐101 (Forge Biologics, Inc) | Intravenous | NCT04693598 (Phase 1/2) |
| AAV | AAVrh.10 | GLB1 | GM1 gangliosidosis | LYS‐GM101 (LYSOGENE) | Intravenous | NCT04273269 (Phase 1/2) |
| AAV | AAV1 | GRN | Frontotemporal dementia | PBFT02 (Passage Bio, Inc.) | Intra cisterna magna | NCT04747431 (Phase 1/2) |
| AAV | AAV1 | NTF3 | Charcot–Marie‐Tooth neuropathy type 1A | scAAV1.tMCK.NTF3 (Nationwide Children's Hospital) | Intramuscular | NCT03520751 (Phase 1/2) |
| AAV | AAV9 | CLN3 | Batten disease | AT‐GTX‐502 (Amicus Therapeutics) | Intrathecal | NCT03770572 (Phase 1/2) |
| AAV | AAV9 | Gigaxonin | Giant axonal neuropathy | scAAv9/JeT‐GAN (National Institute of Neurological Disorders and Stroke) | Intrathecal | NCT02362438 (Phase 1) |
| AAV | AAV5 | HTT | Huntington disease | AMT‐130 (UniQure Biopharma B.V.) | Intrastriatal | NCT04120493 (Phase 1/2) |
| AAV | AAVrh.8 | hHEXA or hHEXB | Tay‐Sachs or Sandhoff disease | AXO‐AAV‐GM2 (Sio Gene Therapies) | Intracisternal/Intrathecal | NCT04669535 (Phase 1) |
| AAV | AAV9 | CLN6 | Variant late‐infantile neuronal ceroid lipofuscinosis | N/A (Medical University of South Carolina) | Intrathecal | NCT02725580 (Phase 1/2) |
| AAV | AAV2 | GDNF | Multiple system atrophy | AT‐GTX‐501 (Amicus Therapeutics) | Putamen infusion | NCT04680065 (Phase 1) |
| Metabolic diseases (n = 27) | ||||||
| AAV | AAV2/6 | IDS | Mucopolysaccharidosis type I (MPS I) | SB‐318 (Sangamo Therapeutics) | Intravenous | NCT02702115 (Phase 1/2) |
| AAV | AAV4D‐C102 | hGLA | Fabry disease | 4D‐310 (4D Molecular Therapeutics) | Intravenous | NCT04519749 (Phase 1/2) |
| AAV | AAV8 | GAA | Pompe disease | AT845 (Audentes Therapeutics) | Intravenous | NCT04174105 (Phase 1/2) |
| AAV | AAV5 | PAH | Phenylketonuria (PKU) | BMN 307 (BioMarin Pharmaceutical) | Intravenous | NCT04480567 (Phase 1/2) |
| AAV | AAV8 | hUGT1A1 | Crigler‐Najjar syndrome | GNT0003 (Genethon) | Intravenous | NCT03466463 (Phase 1) |
| AAV | AAV9 | LAMP2B | Danon disease | RP‐A501 (Rocket Pharmaceuticals Inc.) | Intravenous | NCT03882437 (Phase 1) |
| AAV | AAV8 | G6Pase | Glycogen storage disease type IA | DTX401 (Ultragenyx Pharmaceutical Inc.) | Intravenous | NCT03517085 (Phase 1/2) |
| AAV | AAV8 | OTC | Ornithine transcarbamylase (OTC) deficiency | DTX301 (Ultragenyx Pharmaceutical Inc.) | Intravenous | NCT02991144 (Phase 1/2) |
| AAV | Not specified | ATP7B | Wilson's disease | VTX‐801 (Vivet Therapeutics SAS) | Intravenous | NCT04537377 (Phase 1/2) |
| Hematological diseases (n = 26) | ||||||
| AAV | AAV5 | Factor VIII | Hemophilia A | Valoctocogene Roxaparvovec (BioMarin Pharmaceutical) | Intravenous | NCT04323098 (Phase 3) |
| AAV | AAV2/6 | Factor VIII | Hemophilia A | PF‐07055480 (Pfizer) | Intravenous | NCT03061201 (Phase 2) |
| AAV | AAV Spark10 | Factor IX | Hemophilia B | PF‐06838435 (Pfizer) | Intravenous | NCT03861273 (Phase 3) |
| AAV | AAV5 | Factor IX | Hemophilia B | AMT‐061 (UniQure Biopharma B.V.) | Intravenous | NCT02396342 (Phase 1/2) |
| Musculoskeletal diseases (n = 10) | ||||||
| AAV | AAV9 | Microdystrophin | Duchenne muscular dystrophy | SGT‐001 (Solid Biosciences, LLC) | Intravenous | NCT03368742 (Phase 1/2) |
| AAV | AAV8 | hMTM1 | X‐Linked myotubular myopathy | AT132 (Audentes Therapeutics) | Intravenous | NCT03199469 (Phase 1/2) |
| AAV | AAV.rh74 | β‐Sarcoglycan | Limb‐Girdle muscular dystrophy, type 2E | SRP‐9003 (Sarepta Therapeutics, Inc.) | Intravenous | NCT03652259 (Phase 1/2) |
| Others (n = 5) | ||||||
| AAV | Unknwn | hTERT | Critical limb ischemia | AAV‐hTERT (Libella Gene Therapeutics) | Intravenous | NCT04110964 (Phase 1) |
| AAV | AAV1 | SERCA2a | Congestive heart failure | SRD‐001 (Sardocor Corp.) | Intracoronary | NCT04703842 (Phase 1/2) |
| AAV | AAV2 | Human Aquaporin‐1 | Radiation induced xerostomia or salivary hypofunction | AAV2hAQP1 (MeiraGTx UK II Ltd) | Intraparotidal | NCT02446249 (Phase 1) |
| AAV | AAV8 | VRC07 human monoclonal antibody | HIV‐1 infections with controlled viremia | AAV8‐VRC07) (National Institute of Allergy and Infectious Diseases) | Intramuscular | NCT03374202 (Phase 1) |
| AAV | Unknown | hTERT | Aging | AAV‐hTERT (Libella Gene Therapeutics) | Intravenous | NCT04133649 (Phase 1) |
Abbreviations: Genes of Interest: AADC, aromatic L‐amino acid decarboxylase; ATP7B, Wilson disease protein; CLN6, ceroid‐lipofuscinosis neuronal protein 6; CNGA3, cyclic nucleotide gated channel subunit alpha 3; G6Pase, glucose 6‐phosphatase; GAA, alpha glucosidase; GBA1, glucocerebrosidase; GLB1, galactosidase beta 1; GDNF, glial cell‐derived neurotrophic factor; hAPOE2, human apolipoprotein E; hCYP4V2, human CYP4V2; hGALC, human galactosylceramidase; hGLA, human galactosidase alpha; hHEXA, human hexosaminidase subunit alpha; hHEXB, human hexosaminidase subunit beta; hMTM1, human myotubularin 1; hRS1, human retinoschisin 1; hSMN, human survival motor neuron; hTERT, human telomerase reverse transcriptase; HTT, huntingtin; hUGT1A1, UDP‐glucuronosyltransferase 1‐1; IDS, iduronate 2‐sulfatase; ND4, NADH–ubiquinone oxidoreductase chain 4; LAMP2B, lysosome‐associated membrane protein 2; NTF3, neurotrophin 3; PAH, phenylalanine hydroxylase; OTC, ornithine transcarbamylase;REP1, Rab escort protein 1; RPGR, retinitis Pigmentosa GTPase Regulator; VEGF, vascular endothelial growth factor; sCD59, soluble CD59; SERCA2a, sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a.