Preventing vision loss in a mouse model of Leber Congenital Amaurosis by engineered tRNA.

ABSTRACT: Premature termination codons (PTCs) are associated with rare genetic disorders. Inducing targeted read-through of these 'nonsense mutations' presents a potential therapeutic strategy for modifying disease outcomes. We previously reported that one such PTC, W53X, in the KCNJ13 gene causes blindness and Leber congenital amaurosis type-16 (LCA-16) due to loss of function of the inwardly rectifying potassium channel 7.1 (Kir7.1). Here, we present the proof of concept of a therapeutic approach based on anticodon-engineered transfer RNA (ACE-tRNA). The ACE-tRNA encodes the amino acid tryptophan (Trp) and suppresses the W53X PTC, restoring full-length protein expression. We used helper-dependent adenovirus (HDAd) to deliver the ACE-tRNA^Trp.UAG (tRNA^Trp.UAG) and rescue

SUBMITTER: Akyuz E 

PROVIDER: S-EPMC12265521 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature