• Suppressor tRNAs as personaliz...

Treffer: Suppressor tRNAs as personalized therapy for nonsense mutation-associated pathologies.

Title:
Suppressor tRNAs as personalized therapy for nonsense mutation-associated pathologies.
Authors:
Ignatova Z; Institute of Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany. Electronic address: zoya.ignatova@uni-hamburg.de., Albers S; Institute of Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany. Electronic address: suki.albers@uni-hamburg.de.
Source:
Pharmacology & therapeutics [Pharmacol Ther] 2025 Oct; Vol. 274, pp. 108919. Date of Electronic Publication: 2025 Aug 22.
Publication Type:
Journal Article; Review
Language:
English
Journal Info:
Publisher: Pergamon Press Country of Publication: England NLM ID: 7905840 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-016X (Electronic) Linking ISSN: 01637258 NLM ISO Abbreviation: Pharmacol Ther Subsets: MEDLINE
Imprint Name(s):
Original Publication: Oxford, Elmsford, N. Y., Pergamon Press.
MeSH Terms:
Codon, Nonsense*/genetics , RNA, Transfer*/genetics , RNA, Transfer*/therapeutic use , Precision Medicine*/methods, Humans ; Animals ; Codon, Terminator/genetics
Contributed Indexing:
Keywords: Basket therapeutic approach; RNA-based therapy; Rare diseases; Suppressor tRNA; tRNA engineering; tRNA therapeutics
Substance Nomenclature:
0 (Codon, Nonsense)
9014-25-9 (RNA, Transfer)
0 (Codon, Terminator)
Entry Date(s):
Date Created: 20250824 Date Completed: 20250916 Latest Revision: 20250916
Update Code:
20250916
DOI:
10.1016/j.pharmthera.2025.108919
PMID:
40850535
Database:
MEDLINE

Weitere Informationen

Nonsense mutations - associated with many devastating genetic disorders that currently lack effective treatments - prematurely terminate protein synthesis by converting an amino acid-encoding sense codon into a termination codon. Transfer RNAs (tRNAs), essential players in protein synthesis, have naturally evolved to decode sense codons, while avoiding the three stop codons (UGA, UAG, and UAA) that signal termination of translation. Emerging therapeutic strategies increasingly focus on refactoring natural tRNAs into suppressor tRNAs (sup-tRNAs). These engineered sup-tRNAs recognize nonsense mutation-associated premature stop codons (PTCs), restore translation, and recover protein function. This review summarizes recent advances in the design of sup-tRNAs to decode PTCs and discusses critical milestones in developing sup-tRNAs as a personalized therapeutic approach tailored to individual genetic backgrounds for treating pathologic conditions associated with nonsense mutations.
(Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Declaration of competing interest The authors declare competing interests. Z.I. and S.A. are inventors on patents related to tRNA designs for PTC correction. Z.I. is also a scientific advisor for Tevard Biosciences.