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Engineering the optical control of biology; light-activated DNA.

DNA participates in a multitude of biological processes that govern who we are and how we feel. The regulation of DNA-dependent processes is central to the proper function of living cells as well as molecular biology assays. The directed control of when and where DNA activity takes place is of interest both in clinical gene therapy trials and at the bench in research or diagnostic assays. While many chemical and biochemical compounds have been used to regulate the activity of DNA, most strategies are limited to the aqueous-based diffusion of the activator to the target DNA or cell itself. Louisiana State University's (LSU) Biological and Agricultural Engineering Department is "shedding new light on the topic" by attempting to augment DNA control from the traditional reliance on chemical species to a light-based modulation.

An example of a biological engineering project focused at the cellular and molecular levels, the LSU team chemically blocks DNA by attaching photosensitive cage compounds that can be subsequently activated with light to control DNA function. The attachment of cage compounds to DNA blocks bioactivity until exposed to near-UV light (365 nanometers) that photocleaves the cage, releasing the DNA in its original and bioactive form.

The idea of "caging DNA" was born in the author's graduate mentor's laboratory at Vanderbilt University. Rick Haselton and colleagues noted that, for the past two decades, the caging of smaller molecules (such as adenosine triphosphate and neurotransmitters) had been utilized in biological studies to explore the timing of cell motility, muscle contractility, and kinetics of other intracellular processes. The idea to use cage chemistry to similarly control the timing but also the location of DNA-dependent processes initiated this project.

The author sees potential future application of this light-activated strategy in assisting the realization of genetic therapies in the clinic. Gene therapy is the production of therapeutic products by the body's own cellular machinery. DNA containing the code to produce these products must be introduced into the patient's cells. Successful in vivo gene therapy must both deliver these foreign genes to the specific target cells and restrict this expression to only these target cells.

One potential strategy for targeting expression of introduced genes is the non-specific delivery of "silent" genes followed by reactivation at selected sites. As seen in the illustration below, silent (caged) DNA transgenes could be injected into a patient followed by pinpointed laser light exposure at sites of pathology to activate the therapeutic DNA. This technique could be used to control the timing and location of expressed genes and reduce side effects by restricting production of the therapeutic products to the intended tissues. Ultimately, this biophotonic strategy may offer a new form of engineered control over DNA-dependent processes.


W. Todd Monroe,, Louisiana State University,
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Title Annotation:Focus on Biological Engineering
Author:Monroe, W. Todd
Publication:Resource: Engineering & Technology for a Sustainable World
Date:May 1, 2003
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