Scientists Turn Mammalian Cells Into Complex Biocomputers

sciencehabit quotes a report from Science Magazine: Computer hardware is getting a softer side. A research team has come up with a way of genetically engineering the DNA of mammalian cells to carry out complex computations, in effect turning the cells into biocomputers. The group hasn’t put those modified cells to work in useful ways yet, but down the road researchers hope the new programming techniques will help improve everything from cancer therapy to on-demand tissues that can replace worn-out body parts. To upgrade their DNA “switches,” Wong and his colleagues steered clear of transcription factors and instead switched human kidney cell genes on and off using scissor-like enzymes that selectively cut out snippets of DNA. These enzymes, known as DNA recombinases, recognize two target stretches of DNA, each between 30 to 50 or more base pairs long. When a recombinase finds its target DNA stretches, it cuts out any DNA in between, and stitches the severed ends of the double helix back together. To design genetic circuits, Wong and his colleagues use the conventional cellular machinery that reads out a cell’s DNA, transcribes its genes into RNA, and then translates the RNA into proteins. This normal gene-to-protein operation is initiated by another DNA snippet, a promoter, that sits just upstream of a gene. When a promoter is activated, a molecule called RNA polymerase gets to work, marching down the DNA strand and producing an RNA until it reaches another DNA snippet — a termination sequence — that tells it to stop. To make one of their simplest circuits, Wong’s team inserted four extra snippets of DNA after a promoter. The main one produced green fluorescent protein (GFP), which lights up cells when it is produced. But in front of it was a termination sequence, flanked by two snippets that signaled the DNA recombinase. Wong and his team then inserted another gene in the same cell that made a modified recombinase, activated only when bound to a specific drug; without it, the recombinase wouldn’t cut the DNA. When the promoter upstream of the GFP gene was activated, the RNA polymerase ran headfirst into the termination sequence, stopped reading the DNA, and didn’t produce the fluorescent protein. But when the drug was added, the recombinase switched on and spliced out the termination sequence that was preventing the RNA polymerase from initiating production of GFP. Voila, the cell lit up. The approach Wong and his colleagues used worked so well that they were able to build 113 different circuits, with a 96.5% success rate. The study has been published in the journal Nature.

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