READ THROUGH TRUNCATED PROTEIN IN PREMATURE TERMINATION CODON DISEASES BY USING OPTIMIZED GENE CODON EXPANSION SYSTEM

摘要

Provided is a method for high-efficiently reading through a nonsense mutation site in disease causing genes in monogenic hereditary diseases and recovering a normal structure and a function of a mutant protein, by using a genetic code expansion unnatural amino acid system. By modifying tRNA(tRNAPyl) of ancient methanococcus jannaschii, an all-new unnatural amino acid system that can be high-efficiently read through and that are coded by UAA and UGA, the use range of tRNAPyl and pyrrole lysyl-tRNA synthase (PylRS) orthogonal pairs is expanded. Plasmids simulating endogenous premature termination codon are constructed, so as to evaluate the read-through endogenous premature termination codon. Also provided is a system mainly comprising genes causing monogenichereditary diseases and tumor inhibitory genes in tumor cells.