Figure 1
Main features of gene therapy strategies_
| Non viral | Lentivirus | Adenovirus | Adeno-associated virus | |
|---|---|---|---|---|
| Derived from pathogenic virus | No | Yes | Yes | Yes |
| Size of transgene | No limit | 14kb | 7.5kb | 4.7kb |
| Insertion to host genome (Integration) | No | Yes | No | Rarely |
| Long-lasting gene expression | No | Yes | Yes | Yes |
| Safety issues | No | Insertional mutagenesis | Immune response | Limited immune response |
Indicative list of gene therapy clinical trials for inherited metabolic diseases in 2020_
| Inherited metabolic diseases | Disease | Sponsor | Phase | Status | Vector | NCT number (Clinicaltrials.gov) |
|---|---|---|---|---|---|---|
| Glycogen storage disease 1A | Ultragenyx | I/II | R | AAV8 | NCT035117085 | |
| Crigler-Najjar | Genethon-Selecta Bio | I/II | R | AAV | NCT03466463 | |
| Ornithine transcarbamylase deficiency | University of Pennsylvania | I | T | Adeno- viral | NCT00004498 | |
| Ultragenyx | I/II | R | AAV8 | NCT02991144 | ||
| Intermediary metabolism | Methylmalonic acidaemia | Moderna Therapeutics | I/II | R | Non viral | NCT03810690 |
| Propionic acidaemia | Moderna Therapeutics | I/II | A-NR | Non viral | NCT04159103 | |
| Phenylketonuria | Homology Medicines | I/II | R | AAVH- SC15 | NCT03952156 | |
| National Taiwan University Hospital | I/II | T | AAV2 | NCT01395641 | ||
| Aromatic L-amino acid decarboxylase deficiency | National Taiwan University Hospital | II | R | AAV2 | NCT02926066 | |
| National Institute of Health | I | R | AAV2 | NCT02852213 | ||
| Lipid metabolism | Homozygous Familial | RegenX Bio | I/II | R | AAV | NCT02651675 |
| Sangamo Therapeutics | I/II | H | AAV6 | NCT02702115 | ||
| Mucopolysaccharidosis 1 | RegenX Bio | I | R | AAV9 | NCT03580083 | |
| Orchard Therapeutics/San Raffaele-Telethon Institute for Gene Therapy | I/II | R | LV | NCT03488394 | ||
| Mucopolysaccharidosis 2 | Sangamo Therapeutics | I/II | H | AAV6 | NCT03041324 | |
| RegenX Bio | I/II | R | AAV9 | NCT03566043 | ||
| Manchester University | I/II | R | LV | NCT04201405 | ||
| Lysogene | I/II | T | AAVrh10 | NCT01474343 | ||
| Mucopolysaccharidosis 3A | Lysogene | I/II | R | AAVrh10 | NCT03612869 | |
| Abeona Therapeutics | I/II | R | AAV9 | NCT02716246; NCT04088734 | ||
| Mucopolysaccharidosis 3B | Abeona Therapeutics | I/II | R | AAV9 | NTC03315182 | |
| Uniqure | I/II | T | AAV5 | NCT03300453 | ||
| Mucopolysaccharidosis 6 | Fondazione Telethon | I/II | R | AAV8 | NCT03173521 | |
| Audentes Therapeutics | I/II | A-NR | AAV8 | NCT04174105 | ||
| Spark Therapeutics | I/II | A-NR | AAV | NCT04093349 | ||
| Lysosomal storage diseases | Pompe disease | Florida University | I/II | T | AAV1 | NCT00976352 |
| Florida University | I | R | AAV9 | NCT02240407 | ||
| Danon disease | Rocket Pharmaceuticals | I | R | AAV9 | NCT03882437 | |
| Sangamo Therapeutics | I/II | R | AAV6 | NCT04046224 | ||
| Fabry disease | Freeline Therapeutics | I/II | R | AAV | NCT04040049 | |
| AvroBio | I/II | R | LV | NCT03454893 | ||
| Ceroide lipofuscinosis 6 | Amicus Therapeutics | I/II | A-NR | AAV9 | NCT02725580 | |
| Ceroide lipofuscinosis 3 | Amicus Therapeutics | I/II | R | AAV9 | NCT03770572 | |
| Cornell University | I | A-NR | AAV.rh10 | NCT01161576 | ||
| Ceroide lipofuscinosis 2 | Cornell University | I | A-NR | AAV2 | NCT00151216 | |
| Cornell University | I/II | A-NR | AAV.rh10 | NCT01414985 | ||
| GM1 Gangliosidosis | National Human Genome Research Institute | I/II | R | AAV9 | NCT03952637 | |
| Metachromatic leukodystrophy | Orchard Therapeutics/San Raffaele-Telethon Institute for Gene Therapy | I/II | R | LV | NTC03392987 | |
| Shenzhen University | I/II | R | LV | NCT02559830 | ||
| Gaucher type 1 | AvroBio | I/II | R | LV | NCT04145037 | |
| Bluebird Bio | II/III | A-NR | LV | NCT01896102 | ||
| Peroxisomal disorders | X-linked childhood cerebral adrenoleukodystrophy | Bluebird Bio | III | A-NR | LV | NCT03852498 |
| Shenzhen Second People's Hospital | I/II | R | LV | NCT0372755 |