Not anymore, says Geoffrey von Maltzahn, the CEO of a new startup called Tessera Therapeutics. The company, founded in 2018 by Boston-based biotech investing powerhouse Flagship Pioneering, where von Maltzahn is a general partner, emerged from stealth on Tuesday with $50 million in initial financing. Tessera has spent the past two years developing a new class of molecular manipulators capable of doing lots of things Crispr can do—and some that it can’t, including precisely plugging in long stretches of DNA. It’s not gene editing, says von Maltzahn. It’s “gene writing.”“Simplistically, we think of it as a new category,” says von Maltzahn. “Gene writing is able to make either perfect deletions or simple base pair changes, but its wheelhouse is in the full spectrum, and in particular the ability to make large alterations to the genome.”
To get beyond simplistics, to understand how gene writing works, you have to take a deep dive into the history of an ancient, invisible battle that’s been raging for billions of years.
For nearly as long as there have been bacteria, there have been viruses trying to attack them. These viruses, called phages , are like strings of malicious computer code trying to hack into a bacterial genome to trick it into making more phages. Every day, phages invade and blast apart huge quantities of the world’s bacteria (up to 40 percent of the bacterial population in the oceans alone). To avoid the unrelenting slaughter, bacteria have had to constantly evolve defense systems. Crispr is one of them. It’s a way for bacteria to steal a bit of a phage’s code—its DNA or RNA—and store it in a memory bank, like a primordial immune system. It’s the longest-running arms race in the history of Earth, says Joe Peters, a microbiologist at Cornell University: “That level of evolutionary pressure has driven an incredible amount of novelty in molecular mechanisms for manipulating DNA and RNA.”
But bacteria haven’t just had to contend with foreign viral invaders. Their genomes are also under perpetual assault from within. Through the millennia, as bacteria have been swapping bits of DNA with each other, trying to stay ahead of the next wave of phage attacks, some of those genes evolved the ability to move around and even replicate independently of the rest of their original genome. These so-called “mobile genetic elements,” or MGEs, carry self-contained code for the machinery to either cut and paste or copy and paste themselves into a new locality, either within their host or into nearby bacteria.
