Delivering the goods. Despite the initial promise of gene therapy, which has been in development since 1990, researchers have encountered major roadblocks in using it to find a cure for diseases from Alzheimer’s to uterine cancer. The main obstacle has been devising a safe and effective system to deliver healthy DNA to replace damaged or missing DNA in diseased cells. Two kinds of carriers, or vectors, have generally been used. Engineered virus vectors have proven efficient but as has been clear from some highly publicized incidents, are not completely safe. But synthetic vectors, including a class of molecules known as amphiphiles, have been shown to be nontoxic but inefficient.

Now a team led by Mark Grinstaff, a CAS associate professor of chemistry and an ENG associate professor of biomedical engineering, has engineered a new form of amphiphile vector in which the electrical charge of the vector molecule changes from positive to negative, enhancing the ability of the vector to deliver DNA efficiently.

Amphiphiles are molecules that have both hydrophilic, or water-loving, and hydrophobic, or water-avoiding, parts. The different parts cause them to align with other molecules in predictable ways when dissolved in a solvent. The washing property of soap, for instance, results from amphiphiles within soap that when dissolved in water insert themselves between water and fatty dirt molecules. Amphiphiles also form the main part of cell membranes.

The amphiphile vector designed by Grinstaff and his team initially has a positive charge that helps bind it to the healthy DNA being delivered. After the cell to which the DNA is being delivered engulfs it, the charge is reversed. The negatively charged amphiphile then repels the DNA, releasing it to be incorporated in the host cell DNA.

The researchers found the new vector to be more effective than commercially available synthetic vectors in delivering DNA to Chinese hamster ovarian cells, and the team also has positive preliminary results in human kidney and leukemia cells. According to Grinstaff, “. . . these amphiphiles represent a conceptual departure from the current [vectors] under investigation, and these results are likely to facilitate the design, development, and evaluation of new synthetic non-viral vectors for the delivery of therapeutic DNA.”

This research was reported in the October 6 issue of the Journal of the American Chemical Society.

Prehistoric space weather. An interdisciplinary group of researchers headed by Harlan Spence, a CAS astronomy professor and department chairman, will combine expertise in astronomy, solar physics, space physics, particle physics, geomagnetism, atmospheric physics, and glaciology to examine the history of solar activity over the past 1,000 to 2,000 years and its effects on Earth.

The researchers will analyze Arctic ice for the presence of nitrates, which are produced when major solar events send cosmic rays hurtling through Earth’s atmosphere. When polar ice forms, atmospheric nitrates and other particles and gases are trapped and frozen in it. By measuring nitrate concentrations at various levels of Arctic ice, Spence and his team will determine the nitrate concentrations that existed in the atmosphere at the time the ice was frozen. This information will help them understand the sun’s activity and its effects on Earth’s atmosphere during the period the ice was formed.

The team members will begin with ice created from 1960 to the present. Since there are already good data about space weather during this period, these analyses will allow them to calibrate and validate the research tools that will later be used to analyze ice dating back 2,000 years.

According to Spence, “Our work has the potential to essentially define a new interdisciplinary scientific area within astronomy, space physics, and earth sciences — paleo-solar activity: the study of solar activity over previous millennia as a means to understand not only the sun’s past behavior, but also provide clues as to the sun’s long-term future behavior as a star and its concomitant impacts to Earth.” The results will also provide important information relevant to future space explorations, new understanding for space physics, earth sciences, and atmospheric science and for the development of new aerospace technologies.

This research was originally funded by a SPRInG grant from the Office of the Provost, and is now supported by a Small Grant for Exploratory Research from the National Science Foundation’s Directorate of Geosciences/Division of Atmospheric Sciences Upper Atmosphere Research Section.