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Review
. 2018 Oct 3;3(3):150-158.
doi: 10.1016/j.synbio.2018.09.003. eCollection 2018 Sep.

Therapeutic applications of genetic code expansion

Yujia Huang  1 , Tao Liu  1
Affiliations
Review

Therapeutic applications of genetic code expansion

Yujia Huang et al. Synth Syst Biotechnol. .

Erratum in

  • Erratum regarding previously published articles.
    [No authors listed] [No authors listed] Synth Syst Biotechnol. 2020 Oct 14;5(4):330-331. doi: 10.1016/j.synbio.2020.10.001. eCollection 2020 Dec. Synth Syst Biotechnol. 2020. PMID: 33102827 Free PMC article.

Abstract

In nature, a limited, conservative set of amino acids are utilized to synthesize proteins. Genetic code expansion technique reassigns codons and incorporates noncanonical amino acids (ncAAs) through orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA pairs. The past decade has witnessed the rapid growth in diversity and scope for therapeutic applications of this technology. Here, we provided an update on the recent progress using genetic code expansion in the following areas: antibody-drug conjugates (ADCs), bispecific antibodies (BsAb), immunotherapies, long-lasting protein therapeutics, biosynthesized peptides, engineered viruses and cells, as well as other therapeutic related applications, where the technique was used to elucidate the mechanisms of biotherapeutics and drug targets.

Keywords: Antibody-drug conjugates; Biotherapeutics; Genetic code expansion; Live-attenuated vaccines; Noncanonical amino acids.

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Figures

Fig. 1
Fig. 1
(a) Principles of genetic code expansion technique. aaRS: aminoacyl-tRNA synthetase. (b) Applications of ncAAs in studying protein structures and functions.
Fig. 2
Fig. 2
Coupling reactions used in genetic code expansion. CypK: cyclopropene derivative of lysine; pAcF: p-acetylphenylalanine; NAEK: Nε-2-azideoethyloxycarbonyl-l-lysine; MMAE: monomethyl auristatin E; DIBO: 4-dibenzocyclooctynol; DOTA: 1,4,7,10-tetraazacyclote-tradecane-1,4,7,10-tetraacetic acid; DUPA: 2-[3-(1, 3-dicarboxy propyl)-ureido] pentanedioic acid.
Fig. 3
Fig. 3
Antibody-related applications of an expanded genetic code. scFv: single-chain variable fragment; ncAA: noncanonical amino acid; FITC: fluorescein isothiocyanate; Fab: antigen-binding fragment; TCR: T cell receptor; CAR: chimeric antigen receptor.
Fig. 4
Fig. 4
Applications of genetic code expansion related to viral vectors. aaRS: aminoacyl-tRNA synthetase; ncAA: noncanonical amino acid; AAV: adeno-associated virus; cRGD: cyclic Arg-Gly-Asp; PEG: polyethylene glycols.
Fig. 5
Fig. 5
(a) Principles of live-attenuated vaccines (LAVs) using genetic code expansion. ncAA: noncanonical amino acid. (b) Principles of genetically modified organisms (GMOs).
See this image and copyright information in PMC

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