Tiny technology leads to big changes in DNA research at Argonne

New gene therapy procedures, DNA-based sensors, and other medical applications may be possible using a new method to initiate and control chemical reactions on DNA strands, developed by a team of chemists at the U.S. Department of Energy’s Argonne National Laboratory. The new technology uses specially designed nanometer-sized semiconductors–less than a billionth of an inch in size.

The technology is based on the group’s discovery of “conductive linkers”–small organic molecules that connect the electronic properties of semiconductors to biological or organic molecules. The scientists have used conductive linkers to connect strands of DNA to titanium dioxide crystals measuring only 4.5 nanometers in diameter (a nanometer is about 10,000 times narrower than a human hair).

In the presence of light, a titanium dioxide nanocrystal acts as a semiconductor, generating strong oxidizing power that attacks organic molecules in the same uncontrollable way that laundry bleach attacks all colors in the wash. The researchers found that by using different conductive linkers they can selectively control oxidation.

These nanoparticles have a wide range of potential applications in DNA-based sensing devices. The scientists use the speed of electron transfers to determine the sequence and structure of DNA strands. The four bases that make up DNA are known to have different electronic properties that vary with the sequence and structure of the DNA strand. Guanine is the most readily oxidized, and therefore has the fastest reaction. It is followed, in decreasing order of reactivity, by adenine, cytosine and thymine. By activating the titanium dioxide with light, the team can study the reactions and determine the sequence by comparing the speed and efficiency of the reactions.

The team is part of the Argonne Chemistry Division and includes Chemistry Division Director Marion Thurnauer and chemists Tijana Rajh, David Tiede and Lin Chen. In addition, the team has collaborated with Gayle Woloshak of Northwestern University, formerly of Argonne, to exploit this chemistry for use in gene therapy.

In the body, proteins called restriction enzymes are normally used to recognize and cut defective gene sequences. The researchers have created a novel “artificial restriction enzyme” that can be focused and controlled by light.

For example, a synthetic DNA single strand containing the sequence of a genetic defect can be linked to titanium dioxide. The researchers have shown that the DNA strand will carry the attached titanium dioxide to the cell nucleus, and presumably to the site of the genetic defect on the chromosome. Light will initiate the oxidative chemistry, which clips the defective gene and permits repair with a healthy gene sequence.

The nation’s first national laboratory, Argonne National Laboratory conducts basic and applied scientific research across a wide spectrum of disciplines, ranging from high-energy physics to climatology and biotechnology. Since 1990, Argonne has worked with more than 600 companies and numerous federal agencies and other organizations to help advance America’s scientific leadership and prepare the nation for the future. Argonne is operated by the University of Chicago as part of the U.S. Department of Energy’s national laboratory system.