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Genetic Code Expansion History and Modern Innovations.

Alan Costello1,2, Alexander A Peterson1,2, Pei-Hsin Chen1,2,3

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Genetic code expansion enables incorporating novel amino acids into proteins. This review covers historical and recent advances in in vitro and in vivo methods, highlighting future directions for broader applications.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Synthetic Biology

Background:

  • The genetic code, based on codons specifying 20 proteinogenic amino acids, is fundamental to life.
  • Innovative methods have been developed to expand this repertoire with noncanonical amino acids.
  • Genetic code expansion (GCE) allows for the creation of proteins with novel functionalities.

Purpose of the Study:

  • To review the historical development of in vitro and in vivo genetic code expansion.
  • To highlight recent innovations in expanding the range of accessible monomers and codons.
  • To discuss engineered cellular translation and regulatory improvements for GCE.

Main Methods:

  • Review of scientific literature on genetic code expansion techniques.
  • Summary of advancements in in vitro and in vivo experimental approaches.
  • Analysis of engineered translation systems and regulatory modifications.

Main Results:

  • Significant progress has been made in expanding the genetic code using various innovative approaches.
  • Recent innovations have broadened the scope of biochemically accessible monomers and codons.
  • Engineered cellular translation and regulatory mechanisms have improved GCE efficiency.

Conclusions:

  • Genetic code expansion technologies have advanced significantly, enabling the synthesis of proteins with novel building blocks.
  • Further improvements are needed to overcome current limitations and enhance the scope of GCE.
  • Future strategies will focus on addressing knowledge gaps and developing next-generation GCE technologies.