A tiny Big Deal: Inserting DNA into a single cell

Once in a while it’s important to remind ourselves that not all important advances in science and technology are big (think of the Large Hadron Collider), wide ranging (like stem cell medicine), or controversial (global warming). Sometimes the advances are tiny (physically), quiet (taking place in research centers not in the media mainstream), and incremental (not radical, not totally new, just better). Such an advance is the perfecting of a technique, using femtosecond laser pulses and optoelectronic tweezers, to insert DNA in a single cell – without damage to the cell.

This level of control is, for the moment, unique. Most techniques for transferring DNA material into cells (called transfecting) resemble “gene guns” that literally shoot DNA into a batch of cells, hoping that some of it penetrates individual cells (the blunderbuss method), or holes are punched into a group of cells, which are then placed in a DNA ‘soup’ in hopes that some of the DNA will find its way through the holes. These sorts of methods work, but obviously, they are inefficient, non-specific, and often destructive of cells in unpredictable ways.

Biological scientists have long dreamed of a controlled method for injecting material into individual cells so that the cell is not harmed and the cell can be precisely targeted. The dream was easy, the technology was not. Developed by a team of researchers from South Korea and published in the journal Biomedical Optics Express [01 September 2013, paywalled, Single-cell optoporation and transfection using femtosecond laser and optical tweezers],the two pieces of technology needed to make it work are both derived from lasers, or more generically, optoelectronics. One piece is the so-called femtosecond laser, which produces a beam pulse (electromagnetic pulse) on the order of one femtosecond, that is, 1/100,000,000,000,000 of a second. It means that such a laser can punch a tiny hole into the membrane of a single cell.

Once the femtosecond laser produces the hole, another device, optoelectronic tweezers, picks up a piece of DNA (a plasmid) and pokes it through the hole into the cell. The tweezers use the electromagnetic field generated by a special kind of laser to ‘pick up’ particles. This technique means that a specific piece of DNA can be delivered to precisely identified cells (say, cancer cells).

The researchers verified the technique by using plasmids with DNA that code for a green fluorescent protein. Once inside a cell, the green molecules become visible to optical fluorescence microscopes. The current rate of success for the technique is one is six cells. This is somewhat lower than other techniques, but far more precise in the delivery. The researchers expect the success rate will be improved with further refinements.

It shouldn’t require much imagination to understand that more precise delivery of DNA to specific cells may mean more accurate treatment for cell-based diseases. It will also be a potent technique for testing genetic and medical effectiveness when it becomes routine to insert one gene into a single cell, another gene into another cell, and no gene into a third cell – and compare them. This level of control means a lot to research.

Research Spectrum

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