Safety and Toxicology of Ocular Gene Therapy with Recombinant AAV Vector rAAV.hCNGA3 in Nonhuman Primates.
Hum Gene Ther Clin Dev
; 30(2): 50-56, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-30864850
ABSTRACT
The purpose of this study was to examine the toxicity and side effects of a recombinant adeno-associated virus 8 (AAV8) vector, aimed to treat cyclic nucleotide gated channel alpha 3 (CNGA3)-linked achromatopsia, after a single subretinal administration in cynomolgus macaques. Animals were followed in two studies a 13-week study with 22 animals and a 28-day study with 12 animals. Both groups were divided into subgroups receiving either vehicle only, a low (1 × 1011 vector genomes (vg)), or a high dose (1 × 1012 vg) of rAAV.hCNGA3. In the 13-week study, an extra group received single high-dose intravitreal injections. Here we present the group results of the histological examinations carried out after necropsy from the 28-day study, the retinal functional (electroretinography) in the 13-week study, and clinical observations from both studies. Treatment-related adverse effects were not found, and parameter changes were mostly related to the surgical procedure. The treatment of achromatopsia with rAAV.hCNGA3 is therefore deemed safe to apply to humans.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Defectos de la Visión Cromática
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Canales Catiónicos Regulados por Nucleótidos Cíclicos
Límite:
Animals
Idioma:
En
Revista:
Hum Gene Ther Clin Dev
Año:
2019
Tipo del documento:
Article
País de afiliación:
Alemania