AUTHOR=Paremskaia Anastasiia Iu , Kogan Anna A. , Murashkina Anastasiia , Naumova Daria A. , Satish Anakha , Abramov Ivan S. , Feoktistova Sofya G. , Mityaeva Olga N. , Deviatkin Andrei A. , Volchkov Pavel Yu 

TITLE=Codon-optimization in gene therapy: promises, prospects and challenges

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2024.1371596

DOI=10.3389/fbioe.2024.1371596

ISSN=2296-4185

ABSTRACT=<p>Codon optimization has evolved to enhance protein expression efficiency by exploiting the genetic code’s redundancy, allowing for multiple codon options for a single amino acid. Initially observed in <italic>E. coli</italic>, optimal codon usage correlates with high gene expression, which has propelled applications expanding from basic research to biopharmaceuticals and vaccine development. The method is especially valuable for adjusting immune responses in gene therapies and has the potenial to create tissue-specific therapies. However, challenges persist, such as the risk of unintended effects on protein function and the complexity of evaluating optimization effectiveness. Despite these issues, codon optimization is crucial in advancing gene therapeutics. This study provides a comprehensive review of the current metrics for codon-optimization, and its practical usage in research and clinical applications, in the context of gene therapy.</p>