Brand New ‘TAG’: Scientists Rewrite Genome

I love making German puns (especially when nestled within a Doctor Horrible reference)…

Anyway, a recent bit of news out of Harvard, Yale, and MIT (yes, we’re playing with the big boys today) is an interesting piece of tech that could revolutionize genetic manipulation.

Galleons, I assume you are all familiar with the find-and-replace function common in word processors. The Massachusetts Bay Transportation Authority is all too familiar with it, as they recently made a hilarious mistake on their commuter rail tickets in the month of June. Apparently, they did a find-and-replace on their tickets, replacing “MAY” with “JUN”, which led to:

Good times.

On the whole, however, find-and-replace works quite well. And scientists have found a way to harness this common function and apply the basic concept to changing pieces of a cell’s genome.

Skeptical? You aren’t the only ones.

“We did get some skepticism from biologists early on,” says Peter Carr, senior research staff at MIT’s Lincoln Laboratory. “When you’re making so many intentional changes to the genome, you might think something’s got to go wrong with that.”

However, the researchers have managed to do hundreds of targeted edits of E. coli gene stuffs in living cells, with the altered bacteria behaving normally.

So, how do they do it?

There are four nucleotides involved in the genetic code of most DNA (and you’ll probably recognize, if not their names, then the letters themselves): Adenine, Thymine, Guanine, and Cytosine. When you take three of these nucleotides and put them together in sequence, you get a codon. There are 64 unique codons in the genetic code. On the most basic level, most codons add an amino acid to a growing polypeptide chain, which eventually becomes a protein in the capable hands of our friends, ribosomes. However, some codons (known oh-so-cleverly as stop codons) stop the addition of an amino acid to that chain.

Within E. coli, the TAG stop codon in the rarest (like Mew). Which makes it a prime target for our find-and-replace endeavor. An endeavor that requires some much more specialized tech than your average word processor. After all, it’s not like we can just open up a text file and type in our terms, replacing all with the click of a button:

The first bit of tech is multiplex automated genome engineering (MAGE), which locates specific DNA sequences and replaces them with a new sequence as the cell copies its DNA. Using this, scientists assume direct control of the changes happening within a cell.

The second is conjugative assembly genome engineering (CAGE), which gives them precise control over a process that bacteria use to exchange genetic material, wherein one bacterium builds a little extension/bridge to its neighbor and passes a piece of its genetic material to its new bridgemate.

Specifically, scientists used MAGE to manufacture 32 strains of E. coli in which they replaced 10 of the TAG stop codons with TAA stop codons. But there are 314 total edits required to completely replace all of the TAG codons, so scientists decided to use CAGE to make things a bit simpler.

Basically, they built a playoff bracket for their little bacteria strains, with each one sharing a bit of genetic goodness with one other strain. So, after Round 1 of CAGE, 16 strains were standing, each now containing 20 edits. Then they were put back into CAGE for Round 2, which yielded 8 strains with 40 edits each.

They’ve managed to get their strains down to 4 (with 80 edits in each, roughly a quarter of the total 314 needed), and they believe they’re on track to create that single strain with all of the needed substitutions.

After they’ve managed to substitute all of the TAG codons, they are going to go in and delete the machinery that reads that particular codon. After all, if it doesn’t exist anymore, why should the cell be able to read it? That will free up this slot for a whole new purpose, which scientists can use to encode new amino acids.


But… why? That’s always the question, galleons. While it just sounds cool to muck around in a cell’s genome like that, we all know scientists have to have some ulterior motives when bothering to create such sophisticated technology in an attempt to fine-tune this kind of genetic tampering.

And this is where shit gets scary.

See, with this technology, scientists could engineer bacteria that are resistant to viruses. Because viruses can only infect a cell if the bacterial and viral genetic codes are the same. Change the genetic code and the bacteria suddenly becomes safe from those pesky viruses.

While scientists claim they could also create little genetic firewalls that prevent their engineered bacteria from spreading their genes to natural bacteria (or just prevent them from being able to survive in the wild in general), I’m just saying…

It sounds like we’ve taken our first steps toward the accidental creation of a zombie virus and the subsequent apocalypse.

Galleons, get your shotguns.

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