Structural DNA nanotechnology in living cells

Structural DNA nanotechnology in living cells

Despite the rapid progress of structural DNA nanotechnology, one limitation has been the expense and labor involved to construct complex DNA nanostructures step-by-step in the laboratory. In a collaboration between the laboratories of Hao Yan at the Biodesign Institute at Arizona State University and Nadrian C. Seeman at New York University, two basic structural motifs of DNA nanotechnology have been efficiently and inexpensively replicated in bacterial cells. The fact that these artificial DNA nanostructures are tolerated in living cells was surprising, and may open new avenues for synergism between nanotech and synthetic biology. From Arizona State University , via AAAS EurekAlert “Using living cells as nanotechnology factories“:

In the tiny realm of nanotechnology, scientists have used a wide variety of materials to build atomic scale structures. But just as in the construction business, nanotechnology researchers can often be limited by the amount of raw materials. Now, Biodesign Institute at Arizona State University researcher Hao Yan has avoided these pitfalls by using cells as factories to make DNA based nanostructures inside a living cell.

The results were published in the early online edition of the Proceedings of the National Academy of Sciences [abstract].

Yan specializes in a fast-growing field within nanotechnology — commonly known as structural DNA nanotechnology — that uses the basic chemical units of DNA, abbreviated as C, T, A, or G, to self-fold into a number of different building blocks that can further self-assemble into patterned structures.

“This is a good example of artificial nanostructures that can be replicated using the machineries in live cells” said Yan. “Cells are really good at making copies of double stranded DNA and we have used the cell like a copier machine to produce many, many copies of complex DNA nanostructures.”

DNA nanotechnologists have made some very exciting achievements during the past five to 10 years. But DNA nanotechnology has been limited by the need to chemically synthesize all of the material from scratch. To date, it has strictly been a test tube science, where researchers have developed many toolboxes for making different DNA nanostructures to attach and organize other molecules including nanoparticles and other biomolecules.

“If you need to make a single gram of a DNA nanostructure, you need to order one gram of the starting DNA materials. Scientists have previously used chemical methods to copy branched DNA structures, and there has also been significant work in using long-stranded DNA sequences replicated from cells or phage viruses to scaffold short helper DNA sequences to form 2-D or 3-D objects,” said Yan, who is also a professor in the Department of Chemistry and Biochemistry at ASU.

“We have always dreamed of scaling up DNA nanotechnology. One way to scale that it up is to use the cellular system because simple DNA can be replicated inside the cell. We wanted to know if the cell’s copy machine could tolerate single stranded DNA nanostructures that contain complicated secondary structures.”

To test the nanoscale manufacturing capabilities of cells, Yan and his fellow researchers, Chenxiang Lin, Sherri Rinker and Yan Liu at ASU and their collaborators Ned Seeman and Xing Wang at New York University went back to reproducing the very first branched nanostructure made up of DNA—a cross-shaped, four-arm DNA junction and another DNA junction structure containing a different crossover topology.

To copy these branched DNA nanostructures inside a living cell, the ASU and NYU research team first shipped the cargo inside a bacteria cell. They cut and pasted the DNA necessary to make these structures into a phagemid, a virus-like particle that infects a bacteria cell. Once inside the cell, the phagemid used the cell just like a photocopier machine to reproduce millions of copies of the DNA. By theoretically starting with just a single phagemid infection, and a single milliliter of cultured cells, Yan found that the cells could churn out trillions of the DNA junction nanostructures.

The DNA nanostructures produced in the cells were also found to fold correctly, just like the previously built test tube structures. According to Yan, the results also proved the key existence of the DNA nanostructures during the cell’s routine DNA replication and division cycles. “When a DNA nanostructure gets replicated, it does exist and can survive the complicated cellular machinery. And it looks like the cell can tolerate this kind of structure and still do its job. It’s amazing,” said Yan.

Yan acknowledges that this is just the first step, but foresees there are many interesting DNA variations to consider next. “The fact that the natural cellular machinery can tolerate artificial DNA objects is quite intriguing, and we don’t know what the limit is yet.”

Yan’s group may be able to change and evolve DNA nanostructures and devices using the cellular system and the technology may also open up some possibilities for synthetic biology applications.

“I’m very excited about the future of DNA nanotechnology, but there is a lot of work to be done. An interesting research topic to pursue is the interface of DNA nanostructures with live cells; it is full of opportunities,” said Yan.

Philip Ball provides a more detailed perspective on this research at Nature News “Nanotech comes alive: Viruses and bacteria act as factories for nanostructures“. He quotes other structural DNA nanotechnology researchers on the potential for using Darwinian selection to evolve DNA nanostructures replicated in living cells.

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  1. towery brian October 20, 2008 at 6:53 pm - Reply

    I would like to use this tech to create us ironman suits.



  2. Mr. Darryl Starks October 30, 2008 at 9:34 pm - Reply

    Dear Sir,
    My name is Darryl Starks. I am not an academic, although I have read what I could find on the subjects of nano technology, stem cell research.

    With the daily advancements in these fields as well as others, I wonder how much longer it would be before; with sufficient grant funding of course to engineer nano devices that would go beyond repairing cells, but absorb the cell after it has either re-engineered it, or taken on its function.

    This in turn would, or could cerate an entirely new organism. One that would not have the limitations of life as we know it today. These Neo-Bio-Cybernetic-Organisms would have longer life spans, better health and greater durability.

    Imagine, life forms that would also be upgradeable. As better understanding of the technology and biology developed choices could be taken from across nature to improve the organism.

    I have included examples from news articles of advancements in the fields of nano technology, computer sciences and engineering.

    LONDON (Reuters) – Self-replicating robots are no longer the stuff of science fiction.
    Scientists at the Cornell University in Ithaca, New York have created small robots that can build copies of themselves.

    Each robot consists of several 10-cm (4 inch) cubes which have identical machinery, electromagnets to attach and detach to each other and a computer program for replication. The robots can bend and pick up and stack the cubes.

    “Although the machines we have created are still simple compared with biological self-reproduction, they demonstrate that mechanical self-reproduction is possible and not unique to biology,” Hod Lipson said in a report in the science journal Nature on Wednesday.

    He and his team believe the design principle could be used to make long term, self-repairing robots that could mend themselves and be used in hazardous situations and on space flights.

    The experimental robots, which don’t do anything else except make copies of themselves, are powered through contacts on the surface of the table and transfer data through their faces. They self-replicate by using additional modules placed in special “feeding locations.”

    The machines duplicate themselves by bending over and putting their top cube on the table. Then they bend again, pick up another cube, put it on top of the first and repeat the entire process. As the new robot begins to take shape it helps to build itself.

    “The four-module robot was able to construct a replica in 2.5 minutes by lifting and assembling cubes from the feeding locations,” said Lipson.

    Could this technique be used by the nano device to replicate itself? Four such devices of this kind could scan, repair then duplicate or replace either a living cell that was in place or generate a custom built stemcell that would lay dormant until activated as needed by the organism which would then after activation self-replicate normally as a part of the integrated biological whole.

    Thank you for your time and consideration.


    Mr. Darryl Starks

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