P52 gene, arrows show locations of common mutations 

(Image courtesy www.bioinf.org)

Following on from my last article on using gene therapy for increasing survival in head and neck cancer, Professor Jack Roth, M.D., professor in M. D. Anderson’s Department of Thoracic & Cardiovascular Surgery and colleagues are now focusing on ways to deliver p53 and other tumor-suppressing genes systemically - through intravenous delivery.

The p53 gene is inactivated in many types of cancer. Its normal role is to halt the division of a defective cell and then force the cell to kill itself.

Advexin has to be injected straight into the tumor, but that’s not workable for many cancers. Head and neck cancer kills patients by recurring, not spreading to other organs, but most cancer deaths involve metastasis.

By wrapping tumor-suppressing genes in tiny balls of fat, Roth and colleagues hope to be able to treat more invasive cancers. While p53 nanoparticles are still in preclinical development, those that deliver another tumor-suppressor called FUS1 are in a phase I clinical trial for non-small cell lung cancer. Through 19 patients, the dose escalation study has yet to encounter significant side effects.

Injected nanoparticles gather mainly in tumors, where they are taken up and dissolved, leaving the tumor-suppressor gene at work in the cell. A version that combines FUS1 and p53 is under development.

Elaine Warburton  www.geneticsandhealth.com

GNA 

(Source: John Chaput, University of Arizona)

Nanotechnology researchers are continually on the lookout for new building blocks to push innovation and discovery to scales much smaller than the tiniest speck of dust.  At present DNA nanotechnology researchers are basically limited by what they can buy off the shelf.

In the Biodesign Institute at Arizona State University, researchers led by John Chaput, are building synthetic molecules that assemble like DNA, but have additional properties not found in natural DNA.  It’s called GNA. In the case of GNA, the sugar is the only difference with DNA. The five carbon sugar commonly found in DNA, called deoxyribose, is substituted by glycerol, which contains just three carbon atoms.

In nature, many molecules important to life like DNA and proteins, have evolved to exist only as right-handed. The GNA structures, unlike DNA, turn out to be ‘enantiomeric’ molecules, which in chemical terms means both left and right-handed. The ability to make mirror image structures opens up new possibilities for making nanostructures. The research team also found a number of physical and chemical properties that were unique to GNA, including having a higher tolerance to heat than DNA nanostructures.

Now, with a new material in hand, which John Chaput dubs ‘unnatural nucleic acid nanostructures,’ the group hopes to explore the limits on the topology and types of structure they can make.

http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/2008/130/i18/abs/ja800079j.html

Elaine Warburton  www.geneticsandhealth.com

The Hebrew University of Jerusalem scientists and others have revealed for the first time the electronic structure of single DNA molecules.  In their work, the researchers were able to decode the electronic structure of DNA and to understand how the electrons distribute into the various parts of the double helix, a result that has been pursued by scientists for many years, but was previously hindered by technical problems.

The knowledge that has been acquired in this project may also be relevant for current attempts to develop new sophisticated, reliable, faster and cheaper ways to decode the sequence of human DNA.

Finding the electronic structure of DNA was made possible by a collaboration between experimental and theoretical scientists who worked with long and homogeneous DNA molecules at minus 195 degrees Celsius, using a scanning tunneling microscope (STM) to measure the current that passes across a molecule deposited on a gold substrate. Then, by means of theoretical calculations based on the solution of quantum equations, the electronic structure of DNA corresponding to the measured current was obtained.

The knowledge of the electronic properties of DNA is an important issue in many scientific areas from biochemistry to nanotechnology.  For example, in the study of DNA damage by ultraviolet radiation, UV radiation may cause the generation of free radicals and genetic mutations. In those cases, DNA repair occurs spontaneously via an electronic charge transfer along the DNA helix that restores the damaged molecular bonds.

Elaine Warburton  www.geneticsandhealth.com

Sorry, almost forgot this week’s quote! I’m feeling so miserable from my cold that even this bit of fun got forgotten.

This week’s genetics quote is from Nanoporous Materials: Science and Engineering by GQ Lu, XS Zhao:

The most supervising result of the work is that the DNA molecules do not thread meekly through these nanopores like a noodle of spaghetti that one sucks up, but instead come through the pores in several configurations. This is an important breakthrough towards DNA sequencing, demonstrating the potential applications of nanoporous materials in bioengineering.