Table 1.
Overview of retinal CNG genes, associated human diseases, animal models, preclinical and clinical gene therapy studies. ID, www.clinicaltrials.gov identifier. POC, proof-of-concept.
| Gene (Cell Type) | Associated Human Disease | Animal Models | POC Studies | Preclinical Safety Studies | Clinical Trials (ID) |
|---|---|---|---|---|---|
|
CNGA1 (rods) |
Retinitis pigmentosa, RP49 |
Cnga1 antisense expressing mice: retinal degeneration [53] Canine model (missense mutation): Progressive retinal atrophy [54] |
- | - | - |
|
CNGB1 (rods) |
Retinitis pigmentosa, RP45 |
Cngb1-deficient mice: impaired rod function and retinal degeneration [55,56] Canine model (missense mutation): impaired rod function and retinal degeneration [89] |
[58,90] | - | - |
|
CNGA3 (cones) |
Achromatopsia, ACHM2 |
Cnga3-deficient mice: loss of cone function and cone degeneration [74] cpfl5 mouse: loss of cone function and cone cell degeneration [91] Sheep model (missense mutation): loss of cone function and day blindness [80] |
[76,78,92,93,94,95,96] | [97,98,99,100] |
NCT02610582 NCT02935517 |
|
CNGB3 (cones) |
Achromatopsia, ACHM1 | Canine models (null-deletion or missense mutation): cone degeneration [84] Cngb3-deficient mice: Impaired cone function and cone degeneration [82] |
[101,102,103] | [98,104,105,106] |
NCT02599922 NCT03001310 |