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2022-10-27| R&D

Refactoring Genetic Code to Create a “Firewall” for Bacteria

by Nai Ye Yeat
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By altering the genetic information encoded in DNA, scientists successfully created genetically isolated organisms that cannot exchange genetic information with the environment. This method provides a new paradigm that protects valuable engineered bacteria from natural invaders, such as viral attacks, and safeguards the natural world from engineered genetic material.  

The strategy, published on 20 October in Science and in a preprint posted in July, could shield valuable drug-producing bacteria from invading viruses, which hijack the microbes’ genetic machinery to replicate and destroy the whole batch of drugs.

Related Article: How Are Chromosomes Packed During Cell Division?

How Genetic Information Transfer Destroys Microbes

The genetic code is the rules by which genetic information is encoded in genes within DNA and is near-universal across all kingdoms of life. Various combinations of three DNA nucleotides, called codons, tell a cell which amino acid to install in a protein. The transfer RNAs, or tRNAs, read the codons and bring amino acids to their allocated position. 

As organisms share the common genetic programming language, they can gain new abilities by acquiring genes from other organisms. The common language also allows researchers to insert human genes into bacteria, coaxing the cells to manufacture drugs such as insulin. However, this leaves cells vulnerable to interlopers such as viruses and plasmids, DNA snippets that reproduce inside bacteria and can transport genes.  

Strategies to Stop Viral Attacks

Last year, synthetic biologist Jason Chin of the University of Cambridge and his team swapped out one of the stop codons in E. coli while adding another layer of protection. They replaced two of the codons for the amino acid serine in the microbe’s genome with two different serine codons and later deleted the tRNAs that would recognize the original serine codons. This modified bacterial strain, dubbed Syn61Δ3, could not read two serine codons found in invaders, helping it shrug off bacteria-infecting viruses.  

However, the researchers discovered the strategy was susceptible to 12 types of viruses isolated from various sources, including pig manure and a chicken shed. There are two strategies developed by scientists now. One entails devising tRNAs that actively ruin viral proteins by delivering the wrong amino acids, such as proline and alanine, in response to outsiders’ serine codons. The other would endow Syn61Δ3 with modified tRNAs that misread two of the serine codons carried by invading viruses by inserting leucine instead of serine.

With the new strategies mentioned above, scientists have engineered cells with a genetic firewall isolating synthetic organisms from the environment by refactoring the genetic code. Viral resistance is important, especially when utilizing engineered cells to manufacture drugs and materials, such as insulin, as it may disrupt vital supply chains. Moreover, such genetic firewalls are also particularly important when considering applications outside the laboratory, such as agriculture. 

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