Harvard and MIT researchers develop tech to rewrite genetic code of a living cell

The researchers at Harvard and MIT have come up with a new technology that can rewrite the genetic code of a living cell. This technology will enable editing at the genome level, thus making large-scale changes in the genome of the cell. The scientists believe that this breakthrough technology can help them to design cells that have the ability to build proteins not found naturally and engineer bacteria that can resist any viral infection. Besides this the process can help overwrite a particular DNA sequence all through the genome just like the find-and-replace function in the word processing programs. The researchers can thus use this approach to make numerous edits to the E. coli genome without hindering its function.

Editing the genome

The making:

The research paper is a result of seven-year collaboration between the researchers of the Joseph Jacobson lab, professor of genetics at the Harvard Media School, associate professor of the media lab and George Church. Apart from Carr, other lead authors include Harris Wang, research fellow at Wyss Institute for Biologically Inspired Engineering and Farren Isaacs, assistant professor of molecular, cellular and developmental biology, Yale University.

The DNA has long strings of letters used for coding specific amino acids. The same genetic code is used by every organism to change the letters into the amino acids and then turn to proteins. There are about 64 codons or 3-letter words. Majority of them specify an amino acid while a few of them make the cell to stop the addition of amino acids to the protein chain.

In order to make the edits, the researchers combined two techniques, which are MAGE (multiplex automated genome engineering) and CAGE (conjugative assembly genome engineering). The MAGE is also called the evolution machine because it can accelerate the genetic change in the living cells by locating the specific DNA sequences and replacing them with the new sequence. When the targets are replaced, there is no other change in the rest of the genome. Here, the researchers targeted the stop codon TAG and replaced it with another stop codon TAA in the E. coli. To make the whole process easy, the researchers used the MAGE technology for engineering 32 strains. Each of the strain had 10 codons to be replaced. The researchers then developed CAGE to combine all strains of E. coli and finally get something that has all 314 edits.

Technology for the large-scale editing of DNA

What's new?

• The researchers targeted the stop codons that consist of the letters TAG. The stop codon TAG is very rare in the E. coli genome with only about 314 occurrences. So, it was considered as the main target for the replacement. In order to edit, the researchers combined two different techniques namely MAGE and CAGE.
• MAGE replaces the specific sequences by locating them accurately. Therefore, the scientists can control the type of changes they require in the cells. The targets are replaced and the rest of the genome is untouched. In this particular case, the researchers used another stop codon TAA to replace the TAG stop codons. To manage the process efficiently, they used MAGE to modify 32 strains with each containing 10 TAG codons to be replaced.
• In order to combine the strains to make a single strain with 314 edits, the CAGE technology was developed by the researchers. This helped them to control the naturally occurring process of exchanging the genetic material used by the bacteria. A bacterium passes the genetic material to the neighboring cell be building an extension.
• The scientists were able to engineer bacteria by altering the genetic code. Such bacteria are resistant to multiple viruses. Industries cultivating bacteria could prevent them from being attacked by viruses and enhance the productivity. Viruses infect cells only if they were of the same viral genetic code.
• The genetic firewall created by altering the genetic code prevents the spreading of the genes by the engineered bacteria to the natural environment and allows them to survive in the wild. With the help of the alterations on the living cells, the harmful effects could be easily monitored by the researchers. The altered bacteria, however, showed normal behavior, and could survive and reproduce.

• The code of life can be rewritten with new tools. The existing DNA editing tools are expensive, slow, and difficult to use. The latest tools are fast and efficient in editing the DNA.
• There are three goals from the change.
• First is adding functionality by encoding for useful amino acids in the cells.
• Second is for introducing safety for preventing cross-contamination between the wild and the modified organisms.
• Third one is for establishing multi-viral resistance by rewriting the code used up by the viruses. About 20 percent of the cultures are affected by the viruses in industries like energy and pharmaceuticals that develop bacteria.

The new technology developed by the researchers can be used for overwriting the specific DNA sequences in the whole genome just like the find-and-replace function found in many word processing programs. They can also use this technique for making numerous edits to the E. coli genome without hindering the functioning of the cells.