RW bacteria
Intestinal Chip
The first DNA-based memory device with a rewrite function has been createdDmitry Malianov, "Gazeta.
The device uses the technology of reversible inversion (180 degree unfolding) of certain DNA sections using recombinase enzymes – proteins that cut, flip and recombine DNA sections.
The article "Accumulation and rewriting of digital data in living cells through controlled recombination" (Bonnet et al., Rewritable digital data storage in live cells via engineered control of recombination directionality) with a description of the device was published on Tuesday night Moscow time in Proceedings of the National Academy of Sciences.
The DNA memory cell created at Stanford operates with the genetic equivalent of a bit - a basic binary code that takes two mutually exclusive values: if the DNA section is oriented in one direction, a conditional "zero" is fixed, if in the other – a conditional "one".
The device that records and erases information is a combination of two cloned viral enzymes – integrase and excisionase – borrowed from the bacteriophage Bxb1 (a virus that uses bacterial DNA to replicate its genome).
A drawing from an article in PNAS.
Int – integrase, Xis – excisionase,
GFP and RFP – Green and red fluorescent protein (VM)
The information was recorded on the DNA of E. coli. Under the influence of integrase, the DNA sections of rods with a built-in "fluorescent" gene were cut, turned 180 degrees (inverted) and "sewn" back into the chromosome, and under a purple lamp, the bacteria began to glow red ("one"). Under the action of both integrase and excisionase (cofactor), the site returned to its original position, and the bacteria glowed green ("zero").
These operations did not lead to the death or degeneration of bacteria and were reversible, that is, information on their DNA could be recorded and rewritten many times.
Thus, using the algorithm of "addressing data using recombinase", called the "RAD module" (recombinase addressable data module), it is possible to modify DNA sections – write, erase and write bits on the same chromosomes again.
In order to confidently control the DNA cell, it is necessary to precisely control the modes of interaction of two recombinase factors and cofactors (integrases and excisionases) acting in different directions.
It is known how to modify the desired section of DNA, moreover irreversibly, expressing one specific enzyme. But we had to do this on the same chromosome repeatedly, unfolding the DNA "back and forth". The problem is that if you simultaneously use both enzymes in the wrong proportion, each cell will start to produce its own result, and chaos will come out," explains Jerome Bonnet.
In total, it took three years and 750 attempts to establish the correct proportion of enzymes to accurately control the DNA memory cell: encode, store and erase bits of information in the chromosomes of E. coli.
Eventually, one bit was recorded and preserved in a hundred generations of E. coli, then erased, re-recorded and preserved for another hundred generations.
The next step will be to create a RAD memory that already stores eight bits, or one byte of information. This, of course, will look more spectacular than a DNA device storing one minimal bit, so sooner or later an article will appear in scientific periodicals describing how bioengineers, having recorded Shakespeare's sonnet on E. coli, sent it to colleagues from another laboratory, where the sonnet was considered, erased, and the answer was recorded on the same bacteria and they sent the "DNA letter" back.
However, for the Stanford team, the point of bio-programming is not how fast (the process of writing one bit in the RAD module takes almost a day) and how much information can be written to DNA, but in the development of basic mechanisms that allow managing information inside the cell.
"We are not particularly interested in exactly how this technology will be used: we are only creating sustainable and scalable "biological bits" in order to transfer them into the hands of those who can develop such technologies," explains Bonnet.
Recording information on DNA, for example, can be used for early monitoring of cancer and metastases by installing counters that store the number of cell divisions directly inside cells. To record and store information, viral enzymes and "garbage" sections of human DNA can be used, a significant part of which is nothing more than the same viral genes that infected our ancestors, only now such infection will occur in a targeted way in order to record the necessary bits.
Finally, DNA memory devices will sooner or later complement DNA computers that are making the first progress - for example, liquid DNA processors have already been created that can calculate the square root of a two-digit number.
The future will show exactly how the huge computational potential of biological systems will be used, but for now, as the authors of the article themselves admit, the creation of an 8-bit DNA memory element will require complicating the existing technology by several orders of magnitude, since not two, but several dozen different recombinase factors and cofactors borrowed from different viruses.
Portal "Eternal youth" http://vechnayamolodost.ru22.05.2012