CRISPR editing of anti-anemia drug target rescues independent preclinical models of retinitis pigmentosa.
Cell Rep Med
; 5(4): 101459, 2024 Apr 16.
Article
em En
| MEDLINE
| ID: mdl-38518771
ABSTRACT
Retinitis pigmentosa (RP) is one of the most common forms of hereditary neurodegeneration. It is caused by one or more of at least 3,100 mutations in over 80 genes that are primarily expressed in rod photoreceptors. In RP, the primary rod-death phase is followed by cone death, regardless of the underlying gene mutation that drove the initial rod degeneration. Dampening the oxidation of glycolytic end products in rod mitochondria enhances cone survival in divergent etiological disease models independent of the underlying rod-specific gene mutations. Therapeutic editing of the prolyl hydroxylase domain-containing protein gene (PHD2, also known as Egln1) in rod photoreceptors led to the sustained survival of both diseased rods and cones in both preclinical autosomal-recessive and dominant RP models. Adeno-associated virus-mediated CRISPR-based therapeutic reprogramming of the aerobic glycolysis node may serve as a gene-agnostic treatment for patients with various forms of RP.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retinose Pigmentar
/
Células Fotorreceptoras Retinianas Bastonetes
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2024
Tipo de documento:
Article