Scientists first developed organisms containing six bases
December 01, 2017 Source: Sina Pharmaceutical
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];The DNA of all organisms is tightly controlled by four bases, but the scientists at The Scripps Research Institute (TSRI) and Synthorx miraculously exploited the new technology to make the miracle happen again.
Biotech company Synthorx recently announced that the TSRI Institute and its scientists have successfully developed the first semi-synthetic organism to store and retrieve genetically-added information under the direction of Dr. Floyd Romesberg. The organism can maintain, replicate, transcribe, and translate synthetic DNA base pairs, and express various non-natural amino acids (nnAAs) into the protein.
Synthorx is another step in the path to creating a truly synthetic life. The study, published today in the journal NATURE, breaks through the technical barriers of creating more different proteins that will potentially improve the drug's properties and provide a cost-effective, large-scale environment for drug discovery.
Synthorx scientists have introduced two new bases, and the new technology allows site-specific incorporation of different unnatural amino acids to create new full-length chains and functional proteins. In this paper, scientists used semi-synthetic organisms to create a variant of green fluorescent protein (GFP) and incorporated unnatural amino acids at specific sites. Experiments have shown that semi-synthetic organisms are capable of stably producing full-length variant proteins with similar efficiencies as producing natural proteins.
Dr. Romesberg said: "This is the first time in any cell to produce protein through the decoding of a six-letter genetic alphabet, not just the natural four-letter genetic alphabet. The natural DNA base combinations A, T, G and C limit The types of new protein therapeutics that can be prepared, we have successfully added d5SICSTP and dNaMTP (abbreviated as X and Y) to the genetic alphabet using new techniques, and now we have expanded the number of bases so that we can generate a variety of new The protein is being developed for a wider range of uses, including as a new treatment."
DNA consists of four base pairs called nucleotides: adenine (A) and thymine (T), guanine (G), and cytosine (C). It is only the combination of these four bases that form the genetic material of all life in nature and serve many different purposes, including the coding of amino acid production.
Dr. Romesberg and his team designed another base pair, X and Y, which was previously shown to be stably replicated and maintained by a single-celled organism. Four natural DNA bases are used to encode or spell proteins assembled from 20 natural amino acids. Thanks to the new X and Y, it is now possible to encode an additional 152 new amino acids in principle to prepare proteins with unique pharmacological properties and to improve the safety and efficacy of protein therapeutics.
Dr. Laura Shawver, President and CEO of Synthorx, said: "Protein therapy has brought tremendous value to patients, but there are some limitations with twenty natural amino acids that cannot be corrected. Now we have one Coding and translating semi-synthetic organisms that amplify genetic information, an effective system to design and expand new protein treatments, giving biologics better pharmacological properties, making them more effective, safer and more convenient for patients .
In 2016, Dr. Floyd Romesberg, a founder of the company, and team scientists successfully integrated two synthetic bases into E. coli strains. E. coli also adds mRNA encoding the AXC and GXC codons, as well as DNA encoding the corresponding tRNA. They succeeded in creating an improved tRNA and corresponding amino acids that recognize artificial bases while transporting synthetic amino acids to the ribosome. There, these amino acids are integrated into the proteins expressed by E. coli. At the same time, the researchers also used a variety of detection techniques to prove that there are indeed synthetic amino acids in this protein.
Yorke Zhang, a graduate student at the Doctoral Laboratory in Rome, explains the author: "Semi-synthetic organisms have some built-in safeguards that specifically incorporate a variety of unnatural amino acids into proteins of any size. Peptides to large biologics) and the effective and robust manufacture of these improved protein therapeutics, things that were done in this study were previously impossible."
Dr. Shawver concluded: "This research is a huge technological leap. It will be very valuable for the discovery and development of drugs. Now we can design and manufacture the desired protein therapeutics and create a brand new, individual. Chemicals, this new technology will greatly improve the way we treat diseases." (Sina Pharmaceutical Compilation / Fan Dongdong)
Article Reference Source: Scientist at TSRI and Synthorx Create the First Semi-Synthetic Organism to Encode and Translate Expanded Genetic Information Into a Novel Protein With Different Non-Natural Amino Acids
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