Therapeutic applications of genetic code expansion.

Area of Science:

• Biochemistry and Molecular Biology
• Synthetic Biology
• Biotechnology

Background:

• Proteins are naturally synthesized using a limited set of amino acids.
• Genetic code expansion allows the incorporation of noncanonical amino acids (ncAAs) into proteins.
• This is achieved using orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA pairs to reassign codons.

Purpose of the Study:

• To provide an update on recent advancements in genetic code expansion.
• To highlight the expanding therapeutic applications of this technique.
• To review its use in elucidating biotherapeutic and drug target mechanisms.

Main Methods:

• Utilizing orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA pairs for genetic code expansion.
• Reassigning codons to incorporate noncanonical amino acids (ncAAs).
• Applying genetic code expansion across various therapeutic modalities.

Main Results:

• Significant growth in the diversity and scope of therapeutic applications for genetic code expansion over the past decade.
• Successful application in antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and immunotherapies.
• Use in developing long-lasting protein therapeutics, biosynthesized peptides, and engineered viruses/cells.

Conclusions:

• Genetic code expansion is a powerful and rapidly advancing technology for biotherapeutic development.
• The technique offers novel strategies for creating advanced protein therapeutics and drug delivery systems.
• It also serves as a valuable tool for understanding complex biological mechanisms in drug discovery.