Science

In Central Dogma, the codon sequence, consisting of 3 nucleotides, on the mRNA determines the amino acid sequence on the encoded protein. In nature, 61 codons correspond to 20 amino acid, and 3 codons (UAA, UAG and UGA) are called termination codons (TC). When the translation machinery encounters a termination codon, protein translation stops. 

Transfer RNA (tRNA) is the critical molecule linking the codon on the mRNA and the amino acid on the protein. A tRNA binds a specific aminoacyl-tRNA synthetase in the cytoplasm, leading to addition of a specific amino acid at the 3’ end. The aminoacylated tRNA then enters a ribosome, and when its anticodon sequence is complementary to the codon sequence on the mRNA, its charged amino acid is then added to the growing peptide chain. In nature, no tRNA has an anticodon sequence complementary to the three termination codons, so when the translation machinery encounters a termination codon, protein translation stops.

There are over 10,000 human genetic diseases, and mutations in at least 4,000 genes may directly cause or strongly correlate to a disease. Oncogenesis also strongly correlates with mutations on tumor suppressor genes. 10-15% of such mutations are estimated to be premature termination codons (PTC), causing protein translation to stop early. The resulting truncated proteins often are not stable or functional, leading to diseases. Because there are only 3 types of termination codons, if a therapy can treat the effect of one type of termination codons, it may be developed to treat all diseases caused by this termination codon, regardless of mutation location or specific gene or disease.