Suppressor TRNAs at the Interface of Genetic Code Expansion and Medicine

Overview

Journal Front Genet

Date 2024 May 27

PMID 38798701

Authors

Aya Awawdeh

Alexander A Radecki

Oscar Vargas-Rodriguez

Affiliations

Soon will be listed here.

Abstract

Suppressor transfer RNAs (sup-tRNAs) are receiving renewed attention for their promising therapeutic properties in treating genetic diseases caused by nonsense mutations. Traditionally, sup-tRNAs have been created by replacing the anticodon sequence of native tRNAs with a suppressor sequence. However, due to their complex interactome, considering other structural and functional tRNA features for design and engineering can yield more effective sup-tRNA therapies. For over 2 decades, the field of genetic code expansion (GCE) has created a wealth of knowledge, resources, and tools to engineer sup-tRNAs. In this Mini Review, we aim to shed light on how existing knowledge and strategies to develop sup-tRNAs for GCE can be adopted to accelerate the discovery of efficient and specific sup-tRNAs for medical treatment options. We highlight methods and milestones and discuss how these approaches may enlighten the research and development of tRNA medicines.

Citing Articles

Efficient suppression of premature termination codons with alanine by engineered chimeric pyrrolysine tRNAs.

Awawdeh A, Tapia A, Alshawi S, Dawodu O, Gaier S, Specht C Nucleic Acids Res. 2024; 52(22):14244-14259.

PMID: 39558163 PMC: 11662663. DOI: 10.1093/nar/gkae1048.

Tuning tRNAs for improved translation.

Weiss J, Decker J, Bolano A, Krahn N Front Genet. 2024; 15:1436860.

PMID: 38983271 PMC: 11231383. DOI: 10.3389/fgene.2024.1436860.

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