26rg63
10.3205/26rg63
urn:nbn:de:0183-26rg632
Meeting Abstract
Gene therapy for inherited retinal diseases through activation of silent genes
Mittas
Mittas
David
D
Zürich/CH
author
Gavrilov
Gavrilov
Z.
Z
Zürich/CH
author
Ucambarlic
Ucambarlic
E.
E
Zürich/CH
author
Becirovic
Becirovic
E.
E
Zürich/CH
author
German Medical Science GMS Publishing House
Düsseldorf
610
20260910
engl
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung).
M0658
63
Retinologische Gesellschaft
38. Jahrestagung der Retinologischen Gesellschaft
Grundlagen-Session
Badenweiler
20260703
20260704
26rg63
TextAim: Inherited retinal dystrophies (IRDs) constitute a heterogeneous group of blinding diseases that affect millions of patients worldwide. The most common subtypes include retinitis pigmentosa (RP) and Stargardt disease (STGD). RP can be caused by mutations in over 80 different genes, while STGD is associated almost exclusively with defects in the large ABCA4 gene. Mutations in the MYO7A gene cause the most severe subtype of Usher syndrome (USH1B), a syndromic form of IRDs, leading to combined deafness and blindness due to RP. There is therefore a high unmet medical need for the development of gene-agnostic therapeutic strategies for RP or mutation-independent approaches for the treatment of STGD and RP. Method: Here, we applied CRISPR/Cas-based transcriptional activation (CRISPRa) in combination with CRISPR/Cas genome editing in two mouse models of RP to establish a combinatorial, gene-agnostic therapy for RP based on cellular reprogramming and neuroprotection. Furthermore, we evaluated a novel mutation-agnostic approach for USH1B and STGD by activating genes, which are homologous to Myo7a/Abca4, in the corresponding mouse model. Results: In summary, we provide proof-of-concept for two distinct approaches to the combinatorial, gene-agnostic treatment of RP and the mutation-agnostic treatment of USH1B and STGD in mice. All of which showed significant improvement in mouse models for retinitis pigmentosa and Stargardt disease.Conclusion: Both approaches are the first of their kind and underscore the great therapeutic potential of CRISPRa-mediated epigenome editing.
0
0
0
0